Social brain & ATLAS of Zebra Finch Brain

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stef2cnrs — Sat, 10 Oct 2009 14:02:21 +0000

Publié dans Non classé

E-tools matlab pubmed ; retrieve information from various Web database; read the information into a MATLAB structures.

stef2cnrs — Tue, 06 Oct 2009 13:25:54 +0000

Bioinformatics Toolbox includes several get functions that retrieve information from various Web databases. Additionally, with some basic MATLAB programming skills, you can create your own get function to retrieve information from a specific Web database.

The following procedure illustrates how to create a function to retrieve information from the NCBI PubMed database and read the information into a MATLAB structure. The NCBI PubMed database contains biomedical literature citations and abstracts.

http://www.mathworks.com/access/helpdesk/help/toolbox/bioinfo/index.html?/access/helpdesk/help/toolbox/bioinfo/ug/brschii-1.html

Creating the getpubmed Function

The following procedure shows you how to create a function named getpubmed using the MATLAB Editor. This function will retrieve citation and abstract information from PubMed literature searches and write the data to a MATLAB structure.

Specifically, this function will take one or more search terms, submit them to the PubMed database for a search, then return a MATLAB structure or structure array, with each structure containing information for an article found by the search. The returned information will include a PubMed identifier, publication date, title, abstract, authors, and citation.

The function will also include property name/property value pairs that let the user of the function limit the search by publication date and limit the number of records returned.

From MATLAB, open the MATLAB Editor by selecting File > New > M-File.

Define the getpubmed function, its input arguments, and return values by typing:

function pmstruct = getpubmed(searchterm,varargin)
% GETPUBMED Search PubMed database & write results to MATLAB structure

Add code to do some basic error checking for the required input SEARCHTERM.

% Error checking for required input SEARCHTERM
if(nargin<1)
    error('GETPUBMED:NotEnoughInputArguments',...
          'SEARCHTERM is missing.');
end

Create variables for the two property name/property value pairs, and set their default values.

% Set default settings for property name/value pairs,
% 'NUMBEROFRECORDS' and 'DATEOFPUBLICATION'
maxnum = 50; % NUMBEROFRECORDS default is 50
pubdate = ''; % DATEOFPUBLICATION default is an empty string

Add code to parse the two property name/property value pairs if provided as input.

% Parsing the property name/value pairs
num_argin = numel(varargin);
for n = 1:2:num_argin
    arg = varargin{n};
    switch lower(arg)

        % If NUMBEROFRECORDS is passed, set MAXNUM
        case 'numberofrecords'
            maxnum = varargin{n+1};

        % If DATEOFPUBLICATION is passed, set PUBDATE
        case 'dateofpublication'
            pubdate = varargin{n+1};          

    end
end

You access the PubMed database through a search URL, which submits a search term and options, and then returns the search results in a specified format. This search URL is comprised of a base URL and defined parameters. Create a variable containing the base URL of the PubMed database on the NCBI Web site.
```
% Create base URL for PubMed db site
baseSearchURL = 'http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=search';
```

Create variables to contain five defined parameters that the getpubmed function will use, namely, db (database), term (search term), report (report type, such as MEDLINE^®), format (format type, such as text), and dispmax (maximum number of records to display).

% Set db parameter to pubmed
dbOpt = '&db=pubmed';

% Set term parameter to SEARCHTERM and PUBDATE
% (Default PUBDATE is '')
termOpt = ['&term=',searchterm,'+AND+',pubdate];

% Set report parameter to medline
reportOpt = '&report=medline';

% Set format parameter to text
formatOpt = '&format=text';

% Set dispmax to MAXNUM
% (Default MAXNUM is 50)
maxOpt = ['&dispmax=',num2str(maxnum)];

Create a variable containing the search URL from the variables created in the previous steps.
```
% Create search URL
searchURL = [baseSearchURL,dbOpt,termOpt,reportOpt,formatOpt,maxOpt];
```
Use the urlread function to submit the search URL, retrieve the search results, and return the results (as text in the MEDLINE report type) inmedlineText, a character array.
```
medlineText = urlread(searchURL);
```
Use the MATLAB regexp function and regular expressions to parse and extract the information in medlineText into hits, a cell array, where each cell contains the MEDLINE-formatted text for one article. The first input is the character array to search, the second input is a search expression, which tells the regexp function to find all records that start with PMID-, while the third input, 'match', tells the regexp function to return the actual records, rather than the positions of the records.
```
hits = regexp(medlineText,'PMID-.*?(?=PMID|
```
$)','match');

Instantiate the pmstruct structure returned by getpubmed to contain six fields.

pmstruct = struct('PubMedID','','PublicationDate','','Title','',...
             'Abstract','','Authors','','Citation','');

Use the MATLAB regexp function and regular expressions to loop through each article in hits and extract the PubMed ID, publication date, title, abstract, authors, and citation. Place this information in the pmstruct structure array.

for n = 1:numel(hits)
    pmstruct(n).PubMedID = regexp(hits{n},'(?<=PMID- ).*?(?=\n)','match', 'once');
    pmstruct(n).PublicationDate = regexp(hits{n},'(?<=DP  - ).*?(?=\n)','match', 'once');
    pmstruct(n).Title = regexp(hits{n},'(?<=TI  - ).*?(?=PG  -|AB  -)','match', 'once');
    pmstruct(n).Abstract = regexp(hits{n},'(?<=AB  - ).*?(?=AD  -)','match', 'once');
    pmstruct(n).Authors = regexp(hits{n},'(?<=AU  - ).*?(?=\n)','match');
    pmstruct(n).Citation = regexp(hits{n},'(?<=SO  - ).*?(?=\n)','match', 'once');
end

Select File > Save As.

When you are done, your M-file should look similar to the getpubmed.m file included with the Bioinformatics Toolbox software. The samplegetpubmed.m file, including help, is located at:
```
matlabroot\toolbox\bioinfo\biodemos\getpubmed.m
```

Publié dans e-tools, matlab

zebra finch; search cross-database

stef2cnrs — Tue, 06 Oct 2009 13:00:47 +0000

http://www.ncbi.nlm.nih.gov/sites/gquery?term=finch+or+(Taeniopygia+guttata)

Publié dans web resources on zebra finch

2005; Proposal for Construction of a Physical Map of the Genome of the Zebra Finch

stef2cnrs — Tue, 06 Oct 2009 12:41:22 +0000

Proposal for Construction of a Physical Map of the Genome of the Zebra Finch

(Taeniopygia guttata)

9 January 2005

Proposal for Construction of a Physical Map of the Genome of the Zebra Finch

(Taeniopygia guttata)

9 January 2005

David Clayton, Ph.D., Professor; http://www.life.uiuc.edu/clayton/

Arthur P. Arnold, Ph.D.; http://www.physci.ucla.edu/html/arnold.htm

Wes Warren, Ph.D. ; wwarren@watson.wustl.edu

Jerry Dodgson, Ph.D. ; dodgson@msu.edu

—-

Zebra_finch_genome_white_paper

—

I. Summary

We propose to develop a complete physical map of the zebra finch genome. The zebra finch (ZF) is a model

organism for study of a range of fundamental issues of central relevance to human health and disease. The proposed

genomic map will (1) accelerate and empower research on songbirds, an important surrogate system for testing the

developmental, behavioral and neurological consequences of genetic variation, (2) enrich our understanding of genome

evolution, and 3) enhance the comparative genomics of all avian species to deliver the full promise of the chicken genome

sequence. This project will build on existing NIH-supported resources for ZF genomics, including a BAC library (Tg_Ba,

www.genome.arizona.edu) and growing EST databases. A key element of our strategic rationale is the leveraging of the

recently completed draft sequence of the chicken genome (International Chicken Genome Sequencing Consortium, 2004),

the only avian species sequenced to date. The chicken genome shares sufficient synteny and sequence similarity

(evolutionary distance ~90 MY) to serve as a template for facilitating the alignment and annotation of the ZF genome map.

A high resolution ZF physical map, closely aligned with the chicken sequence, is cost-effective relative to whole genome

sequencing, and will focus subsequent studies of high-interest regions of the ZF genome.

II. Importance of the ZF to biomedical and biological research

A great deal of biological research has centered on songbirds. Nearly half of all avian species are songbirds, and

all songbirds are members of a single monophyletic Order, Passeriformes. This explosion of genetic and species diversity

occurred relatively recently, after the divergence from non-songbirds such as chicken, quail, and pigeon. Songbirds are

readily observed in the wild, and thus during the 20th Century a large amount of information became available about their

behavior, population biology, ecology and evolution. Songbirds figure prominently in research on topics as varied as

stress, reproduction, and endocrinology (Wingfield and Sapolsky, 2003; Wingfield et al., 1997); sperm competition and

genetics of sperm morphology (Birkhead, 1998), evolution of reproductive strategies (K. Arnold et al., 2003), immune

function and environmental toxicology (Snoeijs et al., 2005, Gee et al., 2004), flight physiology (Hambly et al., 2004),

and population and behavioral ecology (Grant et al., 2004). Above all, their greatest importance as a model for

biomedicine, however, derives from their ability to communicate via complex learned vocalizations, an ability not found

in chickens. Indeed, songbirds are one of the few non-human animals that use auditory feedback to learn their

Zebra finch map, page 2

vocalizations, and are held to be the most tractable experimental model for human speech learning (Marler, 1970; Doupe

and Kuhl 1999; Prather and Mooney, 2004; Jarvis, 2004).

By far, the most thoroughly studied single songbird species is the zebra finch (ZF; Taeniogpygia guttata, family

Estrildidae, Suborder Oscines, Order Passeriformes). ZFs are small, have short generation time (4 months) for a complex

vertebrate, and breed easily in captivity. Each ZF male sings a unique learned song as part of the courtship ritual and to

maintain a monogamous bond with his mate. To develop a normal song, the young male must hear both an adult tutor

(typically his father) and his own vocal performance, during a critical period in adolescence. Once the song is learned, it is

sung stably throughout adult life, and new learning ceases.

In 1976 Nottebohm and colleagues described an interconnected circuit in the brain that controls song and song

learning. This circuit comprises a set of large, discrete anatomical nuclei, and it evolved uniquely in songbirds. The

identification of discrete brain nuclei clearly linked to a learned behavior led to a series of path-breaking discoveries that

have strongly shaped the field of neurobiology ever since. Research on songbirds has had a dramatic impact on concepts

of brain development and function in humans because concepts developed first from discoveries on songbirds have been

found subsequently also to be generally true in mammals. The perspective offered from studies of songbirds has often had

unexpected and major impact on understanding of human biology. Some of the seminal discoveries are the following:

Adult neurogenesis. In 1984 Goldman and Nottebohm showed that the adult songbird brain makes new neurons,

in contrast to the universally held belief that neurogenesis does not occur in adults. This discovery catalyzed a

reexamination of the dogma, with the result that it is now realized that specific regions of the mammalian (including

human) brain also make a considerable number of neurons in adulthood. It is fair to say that this discovery has led to a

large shift in the field of neurology. The promise of stem cell biology for treatment of neurological disease was

foreshadowed by Nottebohm’s 1985 book, Hope for a New Neurology. The adult songbird telencephalon remains one of

the few places to study the functional significance and control of adult neurogenesis (Nottebohm, 2004).

Large sex differences in neural structure and function. Large sex differences in the brain of vertebrates were

first discovered from study of the song control nuclei (Nottebohm and Arnold, 1976), catalyzing subsequent discoveries

of morphological sexual dimorphisms in the brain of mammals including humans (e.g., DeLacoste-Utamsing and

Holloway, 1982). The song system became a major model system for understanding sexual differentiation of the brain,

especially the interaction of sex steroid hormones and non-gonadal factors (Agate et al, 2003; Holloway and Clayton,

2001). This system has led to a reconsideration of the forces that lead to sex differences in physiology and disease in

mammals (Arnold, 2004). The 2001 National Institute of Medicine report Exploring the Biological Contributions to

Human Health: Does Sex Matter? (http://www.iom.edu/report.asp?id=5437) argues for gender-specific approaches to

medicine and cites the role of songbird studies in understanding the cellular and molecular forces that shape sex-specific

development.

Influences of steroid hormones on neural networks. Sex steroid hormones cause changes in the synaptic

organization of the adult neural song circuit, a phenomenon first discovered in songbirds (Nottebohm, 1981; DeVoogd

and Nottebohm, 1981) and subsequently found in other circuits in mammals (e.g., Kurz et al., 1986). The songbird is a

model system for understanding changes in the adult brain induced by hormones.

Steroid hormone synthesis in brain. Estrogen is normally thought of as a gonadal steroid, but in ZFs it is

synthesized actively in the brain as well. Recently, estrogen of neural origin has been implicated in causing masculine

patterns of neural development (Holloway and Clayton, 2001), the first time that sex steroids of neural origin have been

directly related to sex differences in neural development (Schlinger et al., 2001). Moreover, the ZF brain has all of the

enzymes needed for de novo synthesis of testosterone and estradiol from cholesterol, similar to steroidogenic cells of the

gonads. The exceptional steroid synthetic capacity of the finch brain makes this system a unique resource for

understanding the roles of brain-derived steroids and for exploring the therapeutic possibilities of manipulating steroid

production in the brain.

The neural basis for learning. The songbird has well-studied auditory and motor pathways adapted for vocal

learning. These pathways are homologous or analogous to those in mammals, including the brain regions involved in

learning of human language (Jarvis 2004). Unlike the human brain, these pathways are amendable to detailed

experimental investigation. In one of the first applications of molecular genetics to songbird biology, Mello et al (1992)

reported that the mere act of listening to tape-recorded birdsong induces a sharp wave of gene expression in brain regions

associated with auditory perception. Moreover, this genomic response changes with song familiarity and context (Mello

et al., 1995, Kruse et al., 2004, Mello, 2002). Meanwhile George et al. (1995) identified a novel gene expressed actively in

the song system only during the critical period for song learning and found the expressed protein to be virtually identical

to human alpha-synuclein, now implicated in Parkinson’s, Alzheimer’s and other neurodegenerative diseases (Clayton and

George, 1998). Other studies on the song system include the first clear example that retinoic acid, the main metabolite of

vitamin A and a morphogen with key roles in embryonic development, is active in the adult brain and regulates the

maturation of a learned behavior (Denisenko-Nehrbass et al., 2000). The FoxP2 gene, critical for human language, is

Zebra finch map, page 3

expressed in the song learning pathway in ZFs at higher levels when learning occurs (Heasler et al. 2004; Teramitsu et

al.,2004). Study of the neurons in the neural circuit offers tremendous advantages for understanding the cellular events

that open critical periods of development and that underlie synaptic plasticity and learning (Brainard and Doupe, 2002).

This system has therefore emerged as one of a small number of model systems for the study of the cellular and molecular

basis of learning.

Complex auditory processing and auditory-motor integration. Songbirds use complex perceptual

mechanisms to interpret sounds, and they match their vocal output to these sounds. They also produce complex sequences

of movements that are amenable to study because of the close mapping of movements and sounds produced. These traits

make songbirds attractive for computational auditory physiologists who study how the brain processes sensory stimuli and

integrates motor commands with perceptual feedback (Margoliash, 1997) and for those who study neural control of motor

sequences (e.g., Hahnloser et al., 2002).

Diversity of songbird species allows for extensive comparative analysis. The great diversity of songbirds

means that numerous traits differ in closely related taxa, allowing species comparisons to illuminate the genetic basis for

differences in physiology, behavior, or population biology.

Thus, as a model for biomedical investigations, the ZF offers an unusual constellation of strengths:

o Discrete brain nuclei for biochemical analysis, infusions, manipulation via genetic vectors, etc.

o Unique behavioral readout relevant to human learning, speech, and auditory-motor integration (learned song

production)

o Potential for neural repair through neurogenesis, steroid signaling, steroidogenesis

o Clear contrasts for study of regulatory biology (sex differences, steroid effects, critical learning periods)

o Interaction of social and environmental factors with neural and genomic responses

o Generation time (4 months) compatible with quantitative genetic analyses

o Opportunity for rich phylogenic comparisons to many other closely related songbird species

III. Resources for further development of the zebra finch model

A. Genetic Strains and Pedigrees.

Zebra finches breed readily in captivity and reach sexual maturity at 4 months. Morphs have been defined based

mostly on color (e.g.,. http://zebrafinch.info/colours/gentech.asp), but there are no fully inbred strains available yet.

Informative mutants have been described, including a half-male half-female lateral gynandromorph, which allowed novel

conclusions about sexual differentiation of the brain (Agate et al., 2003). The Arnold lab is currently studying other

informative mutants such as a bird with male sex chromosomes (ZZ), male brain, and female gonads, and a bird with male

phenotype that carried a W chromosome normally found only in females (ZW). These individual birds offer novel

insights into the role of the sex chromosomes in tissue development. Genetic analysis of the mutants has recently become

much more feasible because of the introduction of techniques for producing metaphase chromosomes from adult tissues

(Itoh and Arnold, 2005), and the availability of the ZF BAC library produced with NHGRI funding in 2002

(www.genome.arizona.edu). The study of individual informative mutants is currently extremely time consuming because

the relevant BAC clones and probes must be isolated by hand, for use as probes in FISH (fluorescent in situ hybridization)

studies of metaphase chromosomes or for identifying genes in areas of chromosome duplication, deletion, or translocation.

Since the 1980s Professor T.R. Birkhead at the University of Sheffield (U.K.), a consultant on this proposal, has

developed a comprehensive 18-generation genealogy (pedigree) of ZFs with blood/tissue samples for about 1,500 birds

from the most recent generations. The goal is to perform detailed analysis of the quantitative genetics of reproductive

traits, in particular to explain the genetic basis for the considerable inter-male variation in sperm phenotypes, and the

maternal effects on sperm morphology and function, which relate to his established research on post-copulatory sexual

selection (sperm competition and cryptic female choice; Forstmeier et at., 2004; Pizzari et al 2003; Birkhead & Pizzari

2003). For the 1,500 birds with DNA samples, data exist for other traits including beak color, body mass, body size and

immune function. Dr. Birkhead also has three lines selected for sperm traits. The value of these genetic resources will be

considerably enhanced if the ZF genome is mapped, and if markers become available for linkage studies.

B. BAC library

Through the NHGRI White Paper mechanism, a ZF BAC library (TG_Ba) was constructed by the Arizona

Genome Institute (http://www.genome.arizona.edu/). The library has an average insert size of 134kb (genome size: 1200

Mb) covering ~16 genome equivalents. It was constructed in the HindIII site of pCUGIBAC1 vector and contains

147,456 clones.

Zebra finch map, page 4

C. EST databases and microarrays

Two large scale songbird transrcriptome/EST efforts are being conducted With the support of NIH RO1

NS045264-03, a normalized cDNA library was prepared from ZF brain RNA (both sexes, multiple ages), and 34,000

clones were 5’-end-sequenced, at the University of Illinois (Keck Center for Comparative and Functional Genomics).

Clustering and contig analysis place these cDNAs into ~18,000 non-redundant sequences. These gene products have been

annotated by BLAST sequence similarity searches against four external databases: TIGR Gallus gallus (chicken) EST,

NCBI chicken unigene, Swissprot, NR.aa. Approximately 76% of these ZF ESTs have highly significant hits against the

chicken EST collection, and ~72% align to the full chicken genome database (ENSEMBL) by BLASTN alignment. High-

quality trimmed sequences have been deposited in Genbank, and both raw and trimmed sequences are available publicly

at http://titan.biotec.uiuc.edu/cgi-bin/ESTWebsite/estima_start?seqSet=songbird. The database is searchable via an

online software interface developed at the Keck Center, called ESTIMA (EST Information Management and Annotation

tool). Via ESTIMA, one can retrieve EST sequence files and annotations by sequence ID, direct BLAST search, Gene

Ontology terms, or keywords from description fields imported from the external databases during the annotation process.

The 18,000 non-redundant ESTs have been spotted on glass microarrays and are now being distributed to the songbird

research community via an organized proposal-and-review process (http://titan.biotec.uiuc.edu/songbird/). A second

resource at the Duke University Medical Center has produced 21 full-length and subtracted cDNA libraries enriched in

sex-specific, developmental, and behaviorally regulated genes (Jarvis et al., 2002). From these libraries, 18,000 cDNA

clones were 5’-and 3’ end-sequenced, which cluster into ~9,000 unique transcripts. An integrative behavior-annotated

cDNA database of these clones is available at http://songbirdtranscriptome.net/. These clones are also on cDNA

microarrays. The full-length clones are useful for transcriptome analysis and for gene over-expression studies. The two

cDNA resources will be integrated to form a superset of ZF ESTs.

D. Gene transfer technologies

Although transgenesis and germline knock-outs have not yet been broadly successful in birds, several labs are

working on this problem (Sang, 2004). In the meantime in vivo gene manipulation has been carried out successfully in

chick embryos using RNAi techniques (Krull, 2004; Bron et al., 2004). These techniques should be easily adapted to

songbirds. The most immediate route for genetic manipulation in the ZF may be via use of genetic expression vectors

and/or RNAi targeted to specific song control nuclei. These techniques can be applied in adult bird to influence function

acutely. Because much of brain development occurs after hatch, gene manipulation is also feasible at many stages of

brain development, including during learning.. Preliminary studies in several labs have demonstrated the feasibility of

several such approaches in the ZF, including injection of naked antisense DNA, lentiviral vectors, adenoviral vectors,

novel nanoparticle carriers, and RNAi. This strategy builds on a long history of targeted pharmacological manipulations

in the song system (e.g., steroids), but will ultimately benefit from, if not require, much more extensive genomic

information (e.g., complete sequence from genes of interest, including regulatory regions from gene promoters).

E. Cytological maps of the ZF genome

Dr. Darren Griffin of Brunel University (UK), a consultant on this application, will submit an application to the

UK Biotechnology and Biological Science Research Council in January 2005, part of which proposes to map ~200 BAC

clones to ZF metaphase chromosomes using FISH. We intend to coordinate our efforts with Dr. Griffin so that the FISH

mapping can be used as an independent check of the physical map generated here, and to help resolve any difficult

portions of the map.

IV. Size of the research community.

A search of the NIH CRISP database in December 2004 indicated that, in the area of songbird research, NIH is

currently funding 46 grants including 37 R01 grants, 13 F30, F31, F32 or K02 awards, 5 R03, R21, or R37 awards, and 4

T32s. A conservative estimate of the yearly funding for these grants is more than $10 million. The numbers of years of

support previously awarded for these currently funded grants is 359 grant-years. Other support comes from the NSF and

non-US granting agencies in Europe and Japan. Because genetic and genomic information has been lacking, these

research programs have been held back in research projects that could be improved through the use of genetic tools for

measurement and manipulation of genes.

The ZF has emerged as one of the top few avian species used as models for biomedical research. A Medline

search for “zebra finch OR taeniopygia OR birdsong OR songbird” retrieves about 2169 papers. In comparison, a search

for “Meleagris”, the genus of the turkey, retrieves about 377, and “quail OR Coturnix” retrieves 7352. The quail and

chicken are quite closely related, and have similar utility in biological research. Songbirds offer an entirely new set of

biological phenomena that are not amenable to study in galliforms such as quail and chickens.

Zebra finch map, page 5

We estimate that about 120-200 labs around the world study songbirds, in the context of neurobiology,

physiology, field biology, evolution, and ecology. Three members of the US National Academy of Sciences (Peter Marler,

Fernando Nottebohm, and Masakazu “Mark” Konishi) have built their careers on the study of song behavior and the

neural circuit controlling song and vocal learning. Other national academy members (e.g., Gordon Orians) have studied

songbird behavior and ecology. Recently we sent an email request to 70 researchers who work on songbirds or other birds,

asking for expressions of interest in this proposal. Forty-seven responded with letters of support. Several are appended to

this proposal. The interest in the ZF genome comes not only from those with specific research interests in songbirds, but

from other avian biologists and comparative geneticists. For example, the letter from Prof. David W. Burt, of the

Department of Genomics and Genetics at the Roslin Institute in Edinburgh (see below), offers to contribute two web

resources: help in mapping ZF genes at the ARK-Genomics website (www.ark-genomics.org) and linking ZF maps with

the chicken and other genomes at www.ensembl.org.

V. Aims, Methods, Budget, and Schedule

Preliminary studies suggest high conservation of the physical map of the genome in birds. When chicken single

chromosome paints are used in other avian species including the ZF (Itoh and Arnold, 2005), they typically hybridize to

one (rarely two) chromosome(s), indicating that despite millions of years of separation, only minor chromosomal

rearrangement has occurred between the chicken and ZF lineages. Moreover, when individual BAC clones from the ZF

are sequenced, they align very closely with homologous regions of the chicken genome, both within and between exons

(Luo et al., in preparation). The similarity of the ZF and chicken genome suggests strongly that the chicken genome can

be used as a template for construction of the physical map of the ZF genome.

Aim 1. Use BAC fingerprinting to develop a clone-based physical map of the ZF genome. We will use the ZF BAC

library (TG_Ba) described above. The WUGSC mapping group uses a high throughput BAC-fingerprinting process based

on restriction digest of BAC clones. This process involves DNA isolation, restriction enzyme digestion and high-

resolution fragment size separation. All clones in the TG_Ba BAC library will be fingerprinted until an attempted total of

10x whole genome coverage is achieved. We will isolate BAC DNA robotically with a 96-well alkaline lysis protocol and

employ high-resolution agarose gel separation of BAC DNA restriction enzyme cleavage products. A high stringency

automated band identification of clone digests will be performed with a WUGSC-modified integrated suite of functions,

written in MATLAB and collectively called BandLeader. Initial assembly parameters of individual clone fingerprints will

be determined empirically. After an optimized initial assembly of the fingerprints is reached, we will refine clone order

within contigs using the automated clone ordering program CORAL. Once clone order is established, potential joins

between contigs are identified by querying the local database with clones at the extreme ends of each contig, at reduced

fingerprint overlap stringency. Fingerprints of clones involved in potential joins will be visually inspected to confirm that

all restriction fragments are logically consistent and the joins made are appropriate. Using this pathfinding process, the

WUGSC has used clone-based physical maps to guide large genome assemblies for several important species, including

Homo sapiens. At later stages of map editing the chicken genome assembly will be used to enhance the merging of

fingerprint contigs.

Aim 2. Establish a minimum tiling path of clones representing the ZF genome. A minimum tiling path will be chosen

using a clone selection application called Minilda. The Minilda method starts with an ordered fingerprint map and chooses

clones to maximize the amount of unique content in each clone selection, minimize excessive overlap, avoid gaps between

adjacent selections when possible, and ignore clones with unusual fingerprints. After clone selection, identified tile path

clones will be rearrayed from their original plates for distribution to the community through the Arizona Genome Institute

(Rod Wing, Director), which made and distributes the BAC library. This rearrayed clone set will all be end sequenced for

more comprehensive end sequence coverage within each fingerprinted contig (Aim 3).

Aim 3. Perform BAC End Sequencing (BES). In project year two, at the close of map construction, BES will

commence on all clones derived from the minimum tile path and selected targets. The predicted 12,000 BESs associated

with the derived tile path will provide high resolution assessments of clone resources for BAC clone sequencing. In

addition, the BES will provide an immediate resource to investigators for gene discovery, marker development and future

linkage map generation. The sequencing process begins with high quality DNA prepared for fingerprinting as described

above and follows these steps:(1) preparation of sequencing reactions; (2) sequence reaction loading and processing on

ABI 3730 sequencing robots; (3) transfer of data to a Unix platform, where the runs enter two different automated queues,

to complete the transfer step and run the XGASP script, the WUGSC pre-processing system; (4) automated transfer of the

data to the WUGSC Oracle database to determine the appropriate destination for each trace; and (5) automated screening

for vector.

Zebra finch map, page 6

Aim 4. Perform overgo hybridization and build a comparative chicken-ZF genome map. We will integrate the ZF

BAC contig map with selected ESTs and build a comparative chicken-ZF genome map by mapping ZF ESTs, BAC end

sequences (Aim 4), and chicken sequences using a high throughput “overgo mapping” strategy.

A. Overgo strategy and methodology. We will link the ZF fingerprint-based BAC contig map to ZF and chicken

genes/sequences via high throughput hybridization using “overgo” probes (Ross et al., 1999). Overlapping synthetic

oligonucleotides will be labeled by Klenow polymerase end-filling. The overgos will then be hybridized in pools to

gridded BAC filters. Since the size and sequence of the probes are completely controlled, the hybridization temperature

can be set to be nearly equal for all probes in any pool, and any known repetitive sequence can be eliminated in advance.

We primarily employ a 4-dimensional pool approach (Romanov et al., 2003). A two-dimensional overgo strategy (e.g.,

Gardiner et al., 2004) presents a feasible alternative, likely to generate BAC-marker assignments more rapidly, but also

more susceptible to errors, since it lacks the built-in redundancy of our strategy.

B. Overgo design. Overgos can be designed from most non-repetitive DNA sequences 200 bp or longer (for details see

Romanov et al., 2003). We check all overgos for repetitive sequences using BLAST. Although we will not be able to

detect ZF-specific repeats, given that there is very little ZF sequence in GenBank, most repeats will be filtered out by

testing against the chicken genome. The majority of repetitive sequences in the chicken genome are ancient LINE-like

CR1-related repeat families, which should also be present in the ZF genome. Alternatively, we will pre-screen overgo

probes to eliminate repetitive ones in advance. We propose to use three types of overgo probes:

1. ZF ESTs. The ESTIMA and songbird transcriptome databases presently contain about 52,000 ZF ESTs

combined, and more are being developed. We will use these sequences to design overgo mapping probes. Most of these

identify a clear orthologue in the chicken genome sequence and can be localized on the chicken map. For ESTs, we will

use sequence information from the 3′ end, where available, as introns are extremely rare in 3′ UTRs (introns that occur by

chance within an overgo sequence are likely to prevent hybridization to genomic DNA), and this region is least likely to

cross-hybridize to other members of a gene family. It will usually be possible to identify 3′ UTR regions of ZF ESTs by

comparison to homologous chicken ESTs.

2. Comparative map chicken overgos. As described below, a high frequency of overgos designed based on

chicken sequences (we have over 1000 chicken overgos already available from previous work) show good hybridization

to ZF BACs. These overgos were chosen from genes and markers already on the chicken linkage map or, in some cases,

chosen to improve the human-chicken comparative map in regions of special interest. The recent availability of the

chicken genome sequence will also allow us to design overgos for comparative mapping in a more systematic fashion, for

example using the “universal” overgo approach (Thomas et al., 2002; Kellner et al., 2004). Many of the initial ZF

fingerprint contigs will subsequently be anchored to the chicken sequence by BAC end sequence homologies. To provide

an independent and complementary set of anchors, we will choose overgo probes spaced throughout the chicken genome.

Overgos will be chosen either from coding or 3′UTR regions of genes, where possible. In “gene desert” regions, overgos

will be chosen from non-coding conserved sequences shown to have very high avian-mammalian similarity (International

Chicken Genome Sequencing Consortium, 2004). We estimate that at least 60-70% of our newly designed chicken

overgos will detect a single ZF BAC fingerprint contig. This method will provide independent evidence anchoring many

BAC contigs to the ZF-chicken comparative map. Since these markers would be evenly spaced, they will assist in

anchoring BAC contigs for which there are fortuitously few BES anchors. More important, since many of these overgo

markers will be gene-based rather than random sequence-based, they will specifically identify the BACs that contain

genes of particular interest. Probes will be included for all specific genes of interest to the songbird community, along

with chicken genes related to endocrinology, reproduction and behavior that are likely to be of interest in songbird

research.

3. Gap filling overgos from ZF BES. In the final phase of this project, we will focus on filling gaps in the ZF

BAC contig map. At this point, we expect to have a preliminary BAC contig map that is anchored to the chicken genome

sequence by both BES matches and overgo analysis. Fingerprint-based contigs are overly conservative in detecting

overlaps. (Two BAC inserts may overlap but generate few (or even no) common restriction fragments. Therefore, they

will not be “called” as overlapping by the software program in order to mitigate against false positive overlap calls.) This

is even true for the second generation chicken BAC contig map that contains only 260 contigs (Wallis et al., 2004). In

many cases, alignment of the BAC contig map to the chicken genome sequence will predict that two adjacent contigs

should either overlap or fall within <100kb of one another (smaller than the size of a typical BAC insert). In these cases,

we will employ end sequences from the terminal BACs of the two contigs that are predicted to overlap or be nearby.

Alternatively, we will use alignment to the chicken genome to predict the segment of chicken sequence that should lie

Zebra finch map, page 7

within the overlap or span the small gap. We will use either the ZF BES sequences or the predicted chicken sequences to

design overgos. Hybridization of such overgos to ZF BAC filters may either confirm the suspected overlap or identify

gap-spanning BACs that were not detected by fingerprinting alone. Since we will have the comparative alignment of our

BAC contigs to the chicken genome, we will prioritize those gaps that appear mostly easily merged, that will merge the

largest, most useful contigs or that lie in a particular region of interest within the chicken and ZF genomes.

C. Preliminary tests of chicken overgos for comparative mapping

The Dodgson lab has performed tests of two types of overgo probes on the TG_Ba BAC clone set. First are

overgos designed using ZF EST sequences, many of which are homologous to chicken Z chromosome genes. As

expected, these appear to be very reliable probes. Although we still have an additional set of hybridizations to do before

full data analysis for all 216 probes can be completed, 72 pooled overgos based solely on ZF ESTs gave 830 positives, or

about 11.5 per probe. Given that many of these overgos are likely on the ZF Z chromosome, and thus may be present at

half the normal rate in the BAC library, this success rate actually exceeds what we had expected, based on the estimated

size of the library. Complete analysis of all of our pool data will likely weed out some false positives in these raw

numbers. The second probe type involves chicken overgo probes, again with almost all of these from the chicken Z

chromosome. A group of 72 pooled chicken probes generated 658 positive ZF BACs or about 9 per overgo. This is about

what we had expected based on the predicted library size. Although the failure rate will surely be a bit higher for chicken

overgos than ZF EST-based overgos, the observed success rate indicates that both existing chicken overgos and future

overgos designed based on the chicken genome sequence will be useful probes, especially in filling gaps in the

comparative ZF-chicken BAC map. Thus, we are confident that chicken overgo probes hybridize well with ZF BACs

despite the ~90 million years of divergent evolution.

Aim 5. Sequence 50 BAC clones of high biological interest. BACs that harbor genomic regions of biological interest

will be selected for sequencing to adequate coverage (~6x). BAC clones will be selected after advertising the availability

of this sequencing service internationally to songbird and other avian biologists, using established email listservs. A short

application will be required from each applicant to explain the biological rationale for the BAC to be sequenced. A

committee, comprising the individuals listed on page one of this proposal, will evaluate the proposals and prioritize the

BACs for sequencing. The BAC sequence will be made available simultaneously to the proposing investigator and on

Genbank. Although the selecting committee itself may propose specific BAC clones, in no case will more than 50% of

the clones selected be those proposed solely by committee members. Our intent is to ensure that the regions of most

interest to the scientific community, broadly defined, are quickly finished and annotated, with minimal duplication of

effort.

Aim 6. Publication of ZF genome map. The WUGSC group has accepted guidelines for the release of all sequence and

mapping data. Any sequence of ZF produced by WUGSC, and all subsequent annotated and improved versions of the

sequences produced by the community, will be provided, without use restrictions, to the scientific community at large for

any and all subsequent research purposes. The raw sequences produced by WUGSC will be deposited into the NCBI

trace archives every night. The assembled and annotated sequences likewise will be available for each BAC assembly as

soon as they have passed quality control. The public will have continuous access to the evolving annotation via the web.

The physical map data will be placed on the WUGSC web site (http://genome.wustl.edu) for easy access via standard FPC

interfaces.

Project Timelines We anticipate that the physical map project could start in September of 2005. Some parts of this

proposed project could start earlier, such as the overgo oligo hybridizations. A map project start date of October 2005

would place total project completion at June of 2006. Therefore, we propose funding this project over a 2 year period.

Benchmark Estimated Completion (months not cumulative)

Aim 1

Isolation of BAC DNAs 4 months

Restriction digestion and sizing of BAC DNAs 5 months

High stringency clone assembly 4 months

Aim 2

Minimum tiling path selection 1 month

Minimum physical genome map BAC set rearraying and archiving 1 month

Aim 3

BAC end sequencing of 12,000 clones = 24,000 ends 1 month

Aim 4

Zebra finch map, page 8

Overgo oligo selection 1 month

Hybridization experiments 4 months

Data analysis 2 months

Aim 5

Selection of BACs by the community 3 months

Sequencing of all selected BACs 4 months

Sequence annotation of all BACs 2 months

Aim 6

Data accessibility for physical maps 1 month

Data accessibility for sequences for BACs 1 month

Budget justification

Activity Unit Description Total estimated costs ($)

library acquisition 1 BAC library 4,608

fingerprinting 110,000 BACs 302,500

BAC end sequencing 12,000 BACs 75,120

MAP construction 4 months 81,284

Overgo hybridizations 1000 probes 61,000

Library rearray 2 months 18,360

Individual BAC sequencing 50 BACs 105,187

Total Project Cost 648,059

VI. Expected benefits of this research

1. Identification of regulatory regions in the genome. Although two large cDNA and EST libraries have been

generated and partially sequenced (http://titan.biotec.uiuc.edu/cgi-bin/ESTWebsite/estima_start?seqSet=songbird and

http://songbirdtranscriptome.net/), neither provides any information on non-transcribed regulatory regions of the genome.

The physical map proposed here will allow any investigator to quickly locate BAC clones encoding most genes of interest,

for further sequencing to identify putative regulatory regions which must be identified for ultimate understanding of the

molecular basis of phenotypes. This information will allow the development of reagents for studying and controlling gene

expression, for driving specific expression of reporters such as Green Fluorescent Protein (GFP), and for marking cells by

their molecular phenotype.

2. Identification of genetic markers. The present proposal will provide the first list of genetic markers for a songbird,

and begin to make feasible linkage studies to study the genetic basis for neural and other traits influenced by mutations or

genetic polymorphisms.

3. A comparative map of the chicken and zebra finch genome. The comparison of the ZF and chicken genome will

allow songbird researchers to make detailed use of the information in the chicken genome sequence. The annotated

chicken genome provides a wealth of candidate genes that may contribute to songbird traits of interest. The aligned

physical map that we propose to generate immediately would allow songbird researchers access to the corresponding

songbird genes, their flanking regulatory regions, and other nearby genes. The relevant ZF BACs can then be employed

in a variety of molecular tests, including transcriptional profiling, chromatin structure and DNA methylation analyses, and

studies of genetic polymorphism. Comparison of other species’ genomes often has demonstrated interesting differences

in the expansion or contraction of linked gene families. The ZF BAC map will facilitate similar comparisons with the

chicken. For example, have gene families that contribute to song behavior undergone expansion and diversification in the

ZF? Additional targeted sequencing of the ZF genome will then allow more detailed chicken/ZF comparisons to be made

and new genetic hypotheses to be generated.

4. Contribution to the study of genome evolution. The comparison of the ZF genome map with other vertebrates will

shed light on the evolution of genomes. In particular, ZF and chicken are phylogenetically distant within the Neognathae

(about 90 My apart, similar to distantly related members of the eutherian mammals), and thus comparisons between these

two should substantially contribute to our understanding of the evolution of most of the ~9600 avian species. As noted

above, many of these species are of major importance to comparative physiology, ecology, evolution, behavior and

endocrinology.

5. Provide a scaffold for subsequent high-throughput genome sequencing of selected regions. The studies outlined

in items 1 to 4 are expected to elucidate larger genome regions that will become of special interest. A likely example

might be those regions of the Z and W chromosome that contribute to sex determination and brain sexual differentiation

(Arnold, 2004). At some point in the future, it likely will prove worthwhile to sequence these larger regions of the ZF

Zebra finch map, page 9

genome. The physical map allows for such an approach in a cost-effective manner, without the need for complete WGS

sequencing of the whole ZF genome.

Other support

To our knowledge there are no other applications for producing a physical map of the ZF genome.

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Zebra finch map, page 11

Letters of Support

To: Art Arnold

From: Fernando Nottebohm

Subject: A physical map of the zebra finch genome: a most welcome project!

Date: Mon, 20 Dec 2004 18:44:14 -0500

Dear Art:

I read with great interest the material you sent me and I am very pleased that you and David Clayton have taken on

the challenge of putting together, with the help of others — Drs. Wesley Warren and Jerry Dodgson — a physical map of

the zebra finch genome. As you know, my laboratory’s work has taken a strong molecular bent as we have begun to

grapple with the molecular events that underlie neuronal replacement in adult brain. Having the physical map on hand,

will not only fuel much comparative work on the genetic evolution of birds and vertebrates in general, but will also make

it easier to focus on specific genes and their promoters.

The brain of songbirds has become fertile material for the study of basic processes of learning and brain repair. In

addition, birds have contributed much to basic issues in development and sexual differentiation. For all of these reasons it

is urgent that there be a fully sequenced and anotated genome of a songbird and its physical layout in the chromosomes. I

think that all of us working on birds will benefit much from the work that you and David Clayton propose to do and hope

it will receive the highest funding priority. I trust that you and David will ensure that the results of this work are made

available to all on prompt and fair terms.

Cordially, Fernando

Dr. Fernando Nottebohm

Professor, Director

Rockefeller University Field Research Center

495 Tyrrel Road

Millbrook, New York 12545

—————————————————————–

Date: Tue, 04 Jan 2005 12:41:29 -0800

To: Art Arnold

From: Peter Marler

Subject: Re: request for letter

Dear Art and David

I was excited to hear about your plans for a grant request to the NHGRI to begin assembling a map of the zebra finch

genome. I hope and pray that you are successful. Now that research on avian vocal learning has become mainstream

neuroscience it is crucial that study of the genetic underpinnings of this unique and highly sophisticated behavior, and the

special brain circuitry that makes it possible, becomes a top priority. The progress with the chicken genome is a major

step forward, setting the stage for comparing in detail the genomes of the two species, one a vocal learner, the other not.

The scientific importance of a project that is focused on this profound behavioral contrast cannot be overstated. The fact

that the chicken and the zebra finch have so much basic neuroanatomy in common should bring into relief the specific

genomic determinants of the brain circuitry required for vocal learning-mechanisms about which a great deal is already

known. This could become a very high yield project., for geneticists and behavioral neurobiologists alike. I wish you

every success with it. Do keep me posted on how it all develops.

With Best Wishes

Peter Marler

Distinguished Professor Emeritus

University of California, Davis

————————————————

6 Jan 2005

Dear Art and David,

Thank you for your recent letter about your plans to submit a grant application to NHGRI to build a physical map

of the zebra finch genome based on the available BAC library. I fully support these plans, which will complement and

extend the usefulness of the recently completed draft of the chicken genome sequence. Based on Zoo-fish studies of

colleagues it is clear that such a map will align will little difficulty with the chicken genome sequence, using the zebra

finch BAC-end sequences. Such a comparison will provide more insight in to the exceptionally stable avian genome,

when compared to the more dynamic mammalian genomes. So this project will add to our knowledge on vertebrate

genome evolution. One of the limitations of the current chicken sequence is the lack of another closely related genome.

For example, with a Zebra finch BAC map we could isolate and sequence genes orthologous to chicken genes, from

Zebra finch map, page 12

which we could identify critical amino acids that confer a positive advantage to a bird – through the application of PAML-

like analyses of synonymous vs. non-synonymous changes. This is not possible at this time between chicken and

mammals due to the 600 million years that separate these extant species. These are only a few of the possible applications

of such a resource.

In addition, I can provide two other resources. ARK-Genomics (www.ark-genomics.org ) is a UK-funded project

and we could provide access to the chicken EST collection, which through hybridisation, provides a rapid means of

mapping genes in the Zebra finch. Together with Manchester University and EBI (Hinxton), the Roslin Institute has

funding from the BBSRC to support the chicken Ensembl database for at least 3 years. We would be able to link the Zebra

finch maps with the chicken and other genomes, thus adding further value to all these projects.

Therefore, I fully support your proposal and wish you success with the application.

Yours sincerely,

Professor David W. Burt

Dept. Genomics and Genetics

Roslin Institute (Edinburgh)

Roslin Midlothian EH25 9PS, UK

E-mail: Dave.Burt@bbsrc.ac.uk

WWW site: http://www.chicken-genome.org/

———————————————

From: John Wingfield

Subject: Zebra finch genome

Date: Fri, 10 Dec 2004 14:53:56 -0800

To: Art Arnold , dclayton@uiuc.edu

Dear Art and David:

I am very happy to support your proposal to move forward with production of a physical map of the zebra finch genome,

with support from the NHGRI. Not only will this will be a valuable resource for songbird researchers , it should make it

easier to link functional studies in songbirds to annotation of related sequences in the human genome, and has the

potential to transform research on how organisms deal with environmental change. In my own research, I anticipate that a

physical map would help me in my studies of environmental control of transitions in life cycles. Of particular interest is

how gene expression changes in response to perturbations of the environment, and how this translates into coping

mechanisms for the organism in the real world. We know a great deal about specific hormonal responses to stress, but

very little about the consequences of stress and how organisms (including humans) recover.

Your project will have a truly major impact on basic research at all levels.

Sincerely,

John C. Wingfield

Professor of Biology

Department of Biology, Box 351800

University of Washington

Seattle Washington 98195

http://faculty.washington.edu/jwingfie

——————————————————

5 January 2005

Arthur P. Arnold, Ph.D.

Professor and Chair

Department of Physiological Science

UCLA

621 Charles E. Young Drive South, Room 4117

Los Angeles CA 90095-1606

Dear Art and David,

I am delighted that you will be submitting a proposal to produce a physical map of the zebra finch genome from the

NHGRI. Given that the draft of the chicken genome has just been completed, a physical map of a songbird would be an

invaluable research tool for comparative genomics. I can imagine a number of ways in which such a map would benefit

my own research. First, I have just submitted a NSRA postdoctoral application with Dr. Chris Balakrishnan to conduct

population genetic analyses of a number of expressed and anonymous (noncoding) loci in Zebra Finches; a physical map

would immediately indicate to us where in the genome these loci are located, and thus considerably improve the quality of

Zebra finch map, page 13

our analyses and our interpretation of correlations in patterns among loci. Part of this proposed research includes

sequencing and population variation analysis of the major histocompatibility complex (MHC). It will be crucial to know

whether the MHC is located on a macro- or microchromosome, and a physical map would be of immediate use in this

regard. Finally, a physical map of zebra finches would allow us and other researchers to understand rates of chromosomal

rearrangement in birds, and to compare these to rates in mammals so as to better understand the forces governing such

rearrangements in different vertebrate groups. Thus a zebra finch map will not only benefit the extensive community of

researchers working with birds, but should be an important advance for vertebrate (and human) genomics generally.

Your proposal has my highest enthusiasm and I hope NHGRI has the vision to support it.

Sincerely,

Scott Edwards

Alexander Agassiz Professor of Zoology

Curator of Ornithology, Museum of Comparative Zoology

Harvard University

Department of Organismic and Evolutionary Biology

26 Oxford Street

Cambridge, Massachusetts 02138 USA

sedwards@fas.harvard.edu

———————————————————–

Date: Mon, 20 Dec 2004 12:04:37 +1100

Subject: Letter of Support

From: Andrew Sinclair

To: Art Arnold

Dear Professor Arnold,

I’m writing in support of your proposal to expand genomic information on the zebra finch.

My research on sex determining genes in the chicken will benefit from having access to a physical map of the zebra finch

genome. Primarily because the degree of similarity between the chicken and zebra finch genomes will allow easy

identification of orthologous genes and most importantly will identify conserved regulatory regions. This type of

comparative analysis is the most efficient way to identify promoter regions of chicken genes. Furthermore, such

comparative analysis will provide insights into avian genome evolution.

Best wishes for this proposal.

A/Professor Andrew Sinclair

Dept of Paediatrics, University of Melbourne

Murdoch Childrens Research Institute

Royal Children’s Hospital

Melbourne Vic 3052 Australia

———————————————-

From: Michael Brainard

Subject: Re: request for letter December 2004

Date: Thu, 9 Dec 2004 11:47:54 -0800

To: Art Arnold , dclayton@uiuc.edu

Dear Art and David,

I am writing to enthusiastically support your proposal to map the zebra finch genome. As evidenced by the burgeoning

number of songbird labs, songbirds have become a premier model system for studying a diverse set of important

neurobiological and neuroendocrine questions (learning and memory, sensorimotor control, sexual dimorphism of brain

and behavior, the role of new neurons, etc…). Zebra finches in turn are the canonical species for these studies. One of the

great advantages of this system has been the ability to combine behavioral, neurophysiological, pharmacological and

anatomical techniques to study a specialized neural system (the ‘song system’) that subserves a neuroethologically

important behavior and that is readily accessible for measurement and manipulation. A number of labs are now

increasingly excited about the prospects of applying genetic techniques to studying songbirds. My own lab, and many

others are beginning to experiment with techniques for in vivo manipulation of genes, using viral infection or in vivo

electroporation. Such experiments will potentially allow us to precisely manipulate molecular events and test their

function in the context of a circuit with a well defined behavioral role. Moreover, monitoring of levels of expression of

different genes in songbirds under differing conditions (stages of development, rearing conditions, etc) is likely to provide

important insights into molecular events that contribute to nervous system function. All of these approaches will be

greatly facilitated by a systematic mapping and subsequent sequencing of the zebra finch genome. Such an undertaking is

hard for any individual laboratory to underwrite, but will be greatly beneficial for the entire birdsong community. It

Zebra finch map, page 14

seems like an ideal enterprise for support by the NHGRI, and I am excited at the prospect that this new resource may

become available for general use. Please let me know if there is anything else that I can to do provide help for this

important undertaking.

best wishes,

Michael S. Brainard

Assistant Professor

Depts. Physiology and Psychiatry

University of California, San Francisco

Room S-762, 513 Parnassus ave.

San Francisco, CA 94143-0444

——————————————————–

Date: Thu, 9 Dec 2004 09:25:24 -0500

To: Art Arnold

From: “John R. Kirn”

Dear Art and David,

I strongly support your work both coordinating, and providing empirical data for a zebra finch genome project. With

the continuing support of the NHGRI, I can see many important applications across avian biology. However, I see much

broader ramifications to the work. Bird studies have impacted virtually all areas of biology (see Konishi et al., 1989

“Contributions of bird studies to biology”, Science 246:465-72), and avian embryological work has laid the foundation for

much of what we know, and continue to learn, about vertebrate development. One can only begin to imagine how

powerful molecular tools, applied to avian biology, will advance science further. My own work centers on understanding

adult neuronal addition and loss which occur throughout the telencephalon in birds, but not mammals. Identifying genes

that regulate this widespread process has obvious implications for stem cell research and potential therapies for brain

repair. Therefore, I see your continuing efforts being of paramount importance for biology and biomedical sciences alike.

Sincerely, John Kirn, Professor, Wesleyan University

—————————————————–

Date: Thu, 09 Dec 2004 13:20:11 -0500

To: Art Arnold

From: Gerry Borgia

Subject: Re: request for letter

Dear Art and David:

I am very pleased to support your proposal NHGRI to map the zebra finch genome. This will be a valuable resource for

students of passerine birds and will provide a foundation for linking many years of behavioral, neurobiological and

developmental work on these birds to modern genomics. The passerine /songbird radiation is of special comparative

interest because it provides a another group to contrast with the mammals and particularly primates in which there has

been rapid brain evolution leading to complex behaviors.

My own work is on sexual selection and mate choice and passerines have been a key group in which many of the most

important discoveries have been made. Genomic information on a passerine will allow entirely new areas to open

integrating genomic information with behavioral and evolutionary studies.

There is a fantastic opportunity here and I sincerely hope this research will be funded.

Best of luck in your endeavors!

Gerald Borgia, Professor

Department of Biology

University of Maryland

College Park, MD 20742-4415

——————————————————-

Date: Thu, 9 Dec 2004 18:48:00 -0600

To: Art Arnold

From: Daniel Margoliash

Subject: Re: request for letter

Dear Art and David:

I have great enthusiasm and strongly support your proposal to move forward with production of a physical map of the

zebra finch genome, with support from the NHGRI. This will be a valuable resource for songbird researchers , and should

make it easier to link functional studies in songbirds to annotation of related sequences in the human genome. Beyond

any application to my own research questions, of which I envision several, I would point out that the song system has

become possibly the premier animal model system for linking cellular and systems level questions in neurobiology with

Zebra finch map, page 15

cognitive and behavioral phenomena. What has been missing from this exceptional mix are the limitations imposed on

molecular studies in an avian model. Your proposal is based on excellent scientific logic, and it also would serve to

protect and enhance an enormous funding commitment the NIH has already made to song bird research.

I wish you the best of luck in your endeavors!

Sincerely,

Daniel Margoliash

Professor, University of Chicago

—————————————————

From: “Harvey J. Karten”

To: “Art Arnold”

Subject: Re: request for letter

Date: Fri, 10 Dec 2004 06:22:05 -0800

Dear Art and David:

I support your proposal with greatest enthusiasm. Avian models of nervous system development have proven of vital

importance in contemporary understanding of spinal cord development, visual system development and organization,

adult neuronogenesis and in a number of other critical areas of neurobiological research. The release of the first draft of

the chicken genome in December will be of vital importance in clarifying fundamental issues in molecular genetics and

the regulatory changes associated with all these areas of research. This single event will serve to accelerate research in

developmental biology beyond all past accomplishments. The prospect of extending this to the Zebra Finch is very

important and exciting. The Zebra Finch is emerging as an experimental subject of vital importance in understanding

complex higher functions related to vocal learning. Recent discoveries in the songbird have revealed that similar genes in

birds and humans are concerned with these functions. My own work on the avian visual and auditory systems will greatly

benefit from this development and facilitate future progress.

I enthusiastically support your proposal to move forward with production of a physical map of the zebra finch genome,

with support from the NHGRI. This will be a valuable resource for songbird researchers, and should make it easier to link

functional studies in songbirds to annotation of related sequences in the human genome. In my own research, I anticipate

that a physical map would help me in my studies of neurotransmitter regulation and morphogenesis in the auditory and

vocal control systems.

Sincerely yours,

Harvey J. Karten, M.D.

Distinguished Professor, University of California

Dept. of Neurosciences UCSD

La Jolla, CA 92093

—————————————–

Date: Fri, 10 Dec 2004 09:46:24 -0600

From: Anton Reiner

Subject: Re: request for letter

To: Art Arnold , david clayton

Dear Art and David,

I thoroughly and enthusiastically support your proposed production of a physical map of the zebra finch genome, and your

plan to seek funding for this endeavor from the NHGRI. Due to the well defined and circumscribed brain regions devoted

to song learning and production in songbirds, songbirds have emerged as major tools for advancing understanding of the

role of the cerebral cortex and basal ganglia in perception of complex sensory stimuli (such as song), in motor learning,

and in the higher order neural coding involved in the production of complex motor patterns (such as song). Given that

zebra finch are the most commonly studied songbirds, progress in defining the zebra finch genome will be of immense

benefit for the full exploitation of the songbird model system, in two general ways. First, mechanistic understanding of

the neural and developmental processes involved in perception, learning and motor control requires understanding of the

molecules involved in the cellular processes underpinning these phenomena. Information on the zebra finch genome will

provide the needed substrate for such molecularly based mechanistic studies. Secondly, the ability to generalize

information from zebra finch song learning and production depends on knowing to what extent the same brain regions and

same molecules are involved as might be involved in mammals. Insight into the zebra finch genome will, again, make it

possible to determine if the molecular fingerprint of brain regions and neural functions devoted to song learning in zebra

finch resembles those in specific brain areas and for specific cortical and basal ganglia functions in mammals. In my own

research, I anticipate that a physical map would aid immensely in my studies of the role of the basal ganglia in song

Zebra finch map, page 16

learning and the resemblance of this to the role of the basal ganglia in motor learning in mammals. I look forward to

progress in your efforts, and greatly appreciate what you are doing for the field of song learning.

Sincerely,

Anton Reiner, Ph.D. Professor

Department of Anatomy & Neurobiology

University of Tennessee Health Science Center

855 Monroe Avenue, Memphis, TN 38163

————————————-

Date: Mon, 20 Dec 2004 12:04:31 +0000

From: “Katherine Buchanan”

To:

Subject: Re: request for letter

Dear Profs Arnold and Clayton,

I am writing to express my enthusiastic support for your proposal to map the zebra finch genome, given support from the

NHGRI. I don’t have to point out to you what a model system the avian songbird brain is for posing both proximate and

ultimate questions relating to neural development, learning processes, the mecahnisms underlying neural function as well

us the evolutionary processes shaping neural design. The zebra finch is without a doubt the best species for this work,

being the avian ‘lab-rat’ of neurobiology. With the investment your labs have made in developing innovative molecular

tools, your proposed approach seems the natural and exciting step in this process. I realise also that this work would

potentially benefit a large number of overseas collaborators and so I wish you every success in your endeavours!

best wishes

Dr Katherine Buchanan

Cardiff School of Biosciences

Cardiff University

Main Building,Park Place

Cardiff CF10 3TL, UK

————————————————–

4 January 2005

Dear Art and David:

I enthusiastically support your proposal to move forward with production of a physical map of the zebra finch genome,

with support from the NHGRI. It will be fantastic to be able to take advantage of genomic approaches in the songbird

system in order to really move ahead on fundamental questions relating to molecular genetics of learned behaviors. This

will be an invaluable resource for songbird researchers, and should make it easier to link functional studies in songbirds to

annotation of related sequences in the human genome. In my own research, I anticipate that a physical map would help

me in studies using stereotaxically targeted recombinant lentiviral infections to manipulate functional expression of

neurotrophic factors such as BDNF.

Best of luck in your endeavors!

Regards,

Sarah Bottjer, Professor

Department of Biological Sciences

University of Southern California

Publié dans web resources on zebra finch

general web resources about zebra finches

stef2cnrs — Tue, 06 Oct 2009 12:34:11 +0000

http://zebrafinch.info/science/

Science

There are a number of people around the world who in some way conduct research into the behavior or biology of zebra finches. A few of these people have web pages you can look at, but please DO NOT contact them with questions about your pet zebra finches – that is not what they are there for. (Go here in stead.)

General web sites, books, etc.

A number of pages have general information about Zebra Finches, as wild birds or as laboratory animals. I suggest you use Dave Runciman’s Zebra Finch Page as a starting point:

The Zebra Finch Page by Dave Runciman, Australia

The Zebra Finch: a Synthesis of Field and Laboratory Studies, (Abstract) by Richard A. Zann

Tim Birkhead

Song learning

By studying Zebra Finch song, scientists hope to learn more about the social effects and causes of Zebra Finch song, as well about learning in general.

The Zebra Finch Song Archive by Heather Williams, USA

Neuroethology: Song Learning in the Zebra Finch

Birds sing in their sleep, BBC News, October 2000

Effects of social context on amplitude in zebra finch vocalizations, (abstract)

Physiology

Studying Zebra Finch physiology can not only help us understand Zebra Finches, but also give insight into other areas, such as the effects of drugs, etc.

Mechanism of Sperm Competition in Birds, Abstract for an article by Tim R. Birkhead published in American Scientist May-June 1996

Hormonal Regulation of Song Behavior in Birds

Model Systems in Neuroethology

Publié dans web resources on zebra finch

zebra finch

stef2cnrs — Tue, 06 Oct 2009 12:30:10 +0000

Other Resources:
Art Arnold Laboratory
The Clayton Lab at Illinois
eFinch.com
Keck Center for Integrative Neuroscience
National Finch and Softbill Society
NetVet
Online Mendelian Inheritance in Animals (OMIA)
Society for Behavioral Neuroendocrinology
The Zebra Finch Page
Zebra Finches
Zebra Finch Society – USA

Publié dans web resources on zebra finch

neurovia download neuro-imaging tools, software brain project; Matlab program package for the analysis of functional neuroimages

stef2cnrs — Wed, 30 Sep 2009 18:26:40 +0000

http://neurovia.umn.edu/incweb/download_home.html

These distribution sets contain software modules and/or data sets extracted from the Visualization and Analysis Software Tools (VAST) library developed at the Minneapolis VA Medical Center, the University of Minnesota and/or the International Consortium for Neuroimaging (INC) (partially funded by the Human Brain Project)

McStrip– a hybrid brain/non-brain stripping algorithm for T1-weighted MR volumes (IDL)
VA Slicer – an adaptation of the SLICER program distributed with IDL 3.1
Corner Cube Environment – a symbolic visualization enviroment [v1.0 added 1999.8.23]
Lyngby toolkit – a Matlab program package for the analysis of functional neuroimages
NU Compare – an IDL toolkit for comparing MRI non-uniformity (or bias) correction algorithms
IDL to MATLAB – allows calling MATLAB functions within an IDL environment
NPAIRS – provides a statistical resampling framework with basic building blocks for benchmarking and comparing pipeline choices using a variety of performance metrics

See also the software distribution page from the Thor Center for Neuroinformatics.

Publié dans atlas, matlab, software

Bibliography of Segmentation in Neuroimaging

stef2cnrs — Wed, 30 Sep 2009 18:14:31 +0000

Bibliography of Segmentation in Neuroimaging

Ref. http://www2.imm.dtu.dk/~fn/bib/Nielsen2001BibSegmentation/Nielsen2001BibSegmentation.html#338

Reference for segmentation in neuroimaging are collected. Both tissue segmentation and parcellation is included.

This structured bibliography is part of a larger collection of bibliographies see . The bibliography is written in L^ATEX and BIBTeX and should be available both as HTML and PostScript.

The bibliography is probably far from complete, but new references are added whenever the author finds new material and has the time to add them. You can email the author if corrections are required or you have found some reference that you fell ought to be included: .

Thanks to , and Arno Klein who provided information. Much of the information in this bibliography is from the SPM mailing list posted by numerous researchers.

This work is or has been funded by the European Union project , the (INC) American Human Brain Project, Danish Research Councils through, the and the .

A list of references is available from

[Harris et al., 2001] parcellation of cortex with brain warping and manual atlas. PMID: 8978636, PMID: 9786148, PMID: 11185422

B. Dawant, S.L. Hartmann, J.-P. Thirion, F. Maes, D. Vandermeulen, P. Demaerel, Automatic 3-D segmentation of internal structures of the head in MR images using a combination of similarity and free-form transformations : part I, methodology and validation on normal subjects , IEEE transactions on medical imaging, vol. 18, no. 10, pp. 909-916, October 1999

Publié dans segmentation, software

digital atlas of zebra finch brain (with skull, head…)

stef2cnrs — Thu, 24 Sep 2009 06:48:30 +0000

1———The cytoarchitectural high resolution atlas of zebra finch brain

http://www.zebrafinch.org/neuroanatomy.html

The cytoarchitectural high resolution atlas of zebra finch brain are under construction through the collabration of Harvey J. Karten, Agnieszka Brzozowska-Prechtl, James Prechtl…

2——————– Nixdorf classic atlas of zebra finch brain

Nixdorf-2007_atlasZebra

3——————– Van der Linden MRI atlas of zebra finch brain and skull

poirier_vanDerLinden2008

4——————–fusion with other data

in progress

Publié dans anatomy, atlas, atlas of zebra finch, bird, brain

pubmed grinvald

stef2cnrs — Mon, 15 Sep 2008 14:40:19 +0000

1: Cereb Cortex. 2007 Dec;17(12):2866-77. Epub 2007 Mar 29. Related Articles, var Menu17395608 = [ ["UseLocalConfig", "jsmenu3Config", "", ""], ["LinkOut", "window.top.location='/sites/entrez?Cmd=ShowLinkOut&Db=pubmed&TermToSearch=17395608&ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstract' ", "", ""] ] –>Links

Cortical response field dynamics in cat visual cortex.

Sharon D, Jancke D, Chavane F, Na’aman S, Grinvald A.

Neurobiology Department, Weizmann Institute of Science, Rehovot 76100, Israel. dahlia@nmr.mgh.harvard.edu

Little is known about the “inverse” of the receptive field–the region of cortical space whose spatiotemporal pattern of electrical activity is influenced by a given sensory stimulus. We refer to this activated area as the cortical response field, the properties of which remain unexplored. Here, the dynamics of cortical response fields evoked in visual cortex by small, local drifting-oriented gratings were explored using voltage-sensitive dyes. We found that the cortical response field was often characterized by a plateau of activity, beyond the rim of which activity diminished quickly. Plateau rim location was largely independent of stimulus orientation. However, approximately 20 ms following plateau onset, 1-3 peaks emerged on it and were amplified for 25 ms. Spiking was limited to the peak zones, whose location strongly depended on stimulus orientation. Thus, alongside selective amplification of a spatially restricted suprathreshold response, wider activation to just below threshold encompasses all orientation domains within a well-defined retinotopic vicinity of the current stimulus, priming the cortex for processing of subsequent stimuli.

Publication Types:

Research Support, Non-U.S. Gov’t

PMID: 17395608 [PubMed - indexed for MEDLINE]

2: Neuroimage. 2007 Jan 1;34(1):94-108. Epub 2006 Oct 25. Related Articles, var Menu17070071 = [ ["UseLocalConfig", "jsmenu3Config", "", ""], ["LinkOut", "window.top.location='/sites/entrez?Cmd=ShowLinkOut&Db=pubmed&TermToSearch=17070071&ordinalpos=2&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstract' ", "", ""] ] –>Links

Independent component analysis of high-resolution imaging data identifies distinct functional domains.

Reidl J, Starke J, Omer DB, Grinvald A, Spors H.

Win Group of Olfactory Dynamics, Heidelberger Akademie der Wissenschaften, Germany.

In the vertebrate brain external stimuli are often represented in distinct functional domains distributed across the cortical surface. Fast imaging techniques used to measure patterns of population activity record movies with many pixels and many frames, i.e., data sets with high dimensionality. Here we demonstrate that principal component analysis (PCA) followed by spatial independent component analysis (sICA), can be exploited to reduce the dimensionality of data sets recorded in the olfactory bulb and the somatosensory cortex of mice as well as the visual cortex of monkeys, without loosing the stimulus-specific responses. Different neuronal populations are separated based on their stimulus-specific spatiotemporal activation. Both, spatial and temporal response characteristics can be objectively obtained, simultaneously. In the olfactory bulb, groups of glomeruli with different response latencies can be identified. This is shown for recordings of olfactory receptor neuron input measured with a calcium-sensitive axon tracer and for network dynamics measured with the voltage-sensitive dye RH 1838. In the somatosensory cortex, barrels responding to the stimulation of single whiskers can be automatically detected. In the visual cortex orientation columns can be extracted. In all cases artifacts due to movement, heartbeat or respiration were separated from the functional signal by sICA and could be removed from the data set. sICA following PCA is therefore a powerful technique for data compression, unbiased analysis and dissection of imaging data of population activity, collected with high spatial and temporal resolution.

Publication Types:

Research Support, Non-U.S. Gov’t

PMID: 17070071 [PubMed - indexed for MEDLINE]

3: Proc Natl Acad Sci U S A. 2005 Oct 4;102(40):14125-6. Epub 2005 Sep 27. Related Articles, var Menu16189023 = [ ["UseLocalConfig", "jsmenu3Config", "", ""], ["Cited Articles" , "window.top.location='/sites/entrez?Db=pubmed&DbFrom=pubmed&Cmd=Link&LinkName=pubmed_pubmed_refs&LinkReadableName=Cited%20Articles&IdsFromResult=16189023&ordinalpos=3&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstract' ", "", ""], ["Compound (MeSH Keyword)" , "window.top.location='/sites/entrez?Db=pccompound&DbFrom=pubmed&Cmd=Link&LinkName=pubmed_pccompound_mesh&LinkReadableName=Compound%20(MeSH%20Keyword)&IdsFromResult=16189023&ordinalpos=3&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstract' ", "", ""], ["Substance (MeSH Keyword)" , "window.top.location='/sites/entrez?Db=pcsubstance&DbFrom=pubmed&Cmd=Link&LinkName=pubmed_pcsubstance_mesh&LinkReadableName=Substance%20(MeSH%20Keyword)&IdsFromResult=16189023&ordinalpos=3&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstract' ", "", ""], ["Free in PMC" , "window.top.location='http://www.pubmedcentral.gov/articlerender.fcgi?tool=pubmed&pubmedid=16189023&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstract&ordinalpos=3' ", "", ""], ["Cited in PMC" , "window.top.location='http://www.pubmedcentral.gov/tocrender.fcgi?action=cited&tool=pubmed&pubmedid=16189023&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstract&ordinalpos=3' ", "", ""], ["LinkOut", "window.top.location='/sites/entrez?Cmd=ShowLinkOut&Db=pubmed&TermToSearch=16189023&ordinalpos=3&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstract' ", "", ""] ] –>Links

Comment on:

Proc Natl Acad Sci U S A. 2005 Sep 27;102(39):14063-8.

Imaging input and output dynamics of neocortical networks in vivo: exciting times ahead.

Grinvald A.

Department of Neurobiology, The Weizmann Institute of Science, 76100 Rehovot, Israel. amiram.grinvald@weizmann.ac.il

Publication Types:

Comment

PMID: 16189023 [PubMed - indexed for MEDLINE]

PMCID: PMC1242320

4: J Neurosci. 2005 Mar 2;25(9):2233-44. Related Articles, var Menu15745949 = [ ["UseLocalConfig", "jsmenu3Config", "", ""], ["Compound (MeSH Keyword)" , "window.top.location='/sites/entrez?Db=pccompound&DbFrom=pubmed&Cmd=Link&LinkName=pubmed_pccompound_mesh&LinkReadableName=Compound%20(MeSH%20Keyword)&IdsFromResult=15745949&ordinalpos=4&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstract' ", "", ""], ["Substance (MeSH Keyword)" , "window.top.location='/sites/entrez?Db=pcsubstance&DbFrom=pubmed&Cmd=Link&LinkName=pubmed_pcsubstance_mesh&LinkReadableName=Substance%20(MeSH%20Keyword)&IdsFromResult=15745949&ordinalpos=4&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstract' ", "", ""], ["Cited in PMC" , "window.top.location='http://www.pubmedcentral.gov/tocrender.fcgi?action=cited&tool=pubmed&pubmedid=15745949&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstract&ordinalpos=4' ", "", ""], ["LinkOut", "window.top.location='/sites/entrez?Cmd=ShowLinkOut&Db=pubmed&TermToSearch=15745949&ordinalpos=4&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstract' ", "", ""] ] –>Links

Compartment-resolved imaging of activity-dependent dynamics of cortical blood volume and oximetry.

Vanzetta I, Hildesheim R, Grinvald A.

Department of Neurobiology, Weizmann Institute of Science, Rehovot 76100, Israel. ivo.vanzetta@incm.cnrs-mrs.fr

Optical imaging, positron emission tomography, and functional magnetic resonance imaging (fMRI) all rely on vascular responses to image neuronal activity. Although these imaging techniques are used successfully for functional brain mapping, the detailed spatiotemporal dynamics of hemodynamic events in the various microvascular compartments have remained unknown. Here we used high-resolution optical imaging in area 18 of anesthetized cats to selectively explore sensory-evoked cerebral blood-volume (CBV) changes in the various cortical microvascular compartments. To avoid the confounding effects of hematocrit and oximetry changes, we developed and used a new fluorescent blood plasma tracer and combined these measurements with optical imaging of intrinsic signals at a near-isosbestic wavelength for hemoglobin (565 nm). The vascular response began at the arteriolar level, rapidly spreading toward capillaries and venules. Larger veins lagged behind. Capillaries exhibited clear blood-volume changes. Arterioles and arteries had the largest response, whereas the venous response was smallest. Information about compartment-specific oxygen tension dynamics was obtained in imaging sessions using 605 nm illumination, a wavelength known to reflect primarily oximetric changes, thus being more directly related to electrical activity than CBV changes. Those images were radically different: the response began at the parenchyma level, followed only later by the other microvascular compartments. These results have implications for the modeling of fMRI responses (e.g., the balloon model). Furthermore, functional maps obtained by imaging the capillary CBV response were similar but not identical to those obtained using the early oximetric signal, suggesting the presence of different regulatory mechanisms underlying these two hemodynamic processes.

Publication Types:

PMID: 15745949 [PubMed - indexed for MEDLINE]

5: Nat Rev Neurosci. 2004 Nov;5(11):874-85. Related Articles, var Menu15496865 = [ ["UseLocalConfig", "jsmenu3Config", "", ""], ["Cited in PMC" , "window.top.location='http://www.pubmedcentral.gov/tocrender.fcgi?action=cited&tool=pubmed&pubmedid=15496865&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstract&ordinalpos=5' ", "", ""], ["LinkOut", "window.top.location='/sites/entrez?Cmd=ShowLinkOut&Db=pubmed&TermToSearch=15496865&ordinalpos=5&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstract' ", "", ""] ] –>Links

VSDI: a new era in functional imaging of cortical dynamics.

Grinvald A, Hildesheim R.

Department of Neurobiology, The Weizmann Institute of Science, Rehovot, 76100 Israel. Amiram.Grinvald@weizmann.ac.il

During the last few decades, neuroscientists have benefited from the emergence of many powerful functional imaging techniques that cover broad spatial and temporal scales. We can now image single molecules controlling cell differentiation, growth and death; single cells and their neurites processing electrical inputs and sending outputs; neuronal circuits performing neural computations in vitro; and the intact brain. At present, imaging based on voltage-sensitive dyes (VSDI) offers the highest spatial and temporal resolution for imaging neocortical functions in the living brain, and has paved the way for a new era in the functional imaging of cortical dynamics. It has facilitated the exploration of fundamental mechanisms that underlie neocortical development, function and plasticity at the fundamental level of the cortical column.

Publication Types:

PMID: 15496865 [PubMed - indexed for MEDLINE]

6: Neuroimage. 2001 Jun;13(6 Pt 1):959-67. Related Articles, var Menu11352602 = [ ["UseLocalConfig", "jsmenu3Config", "", ""], ["Cited in PMC" , "window.top.location='http://www.pubmedcentral.gov/tocrender.fcgi?action=cited&tool=pubmed&pubmedid=11352602&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstract&ordinalpos=6' ", "", ""], ["LinkOut", "window.top.location='/sites/entrez?Cmd=ShowLinkOut&Db=pubmed&TermToSearch=11352602&ordinalpos=6&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstract' ", "", ""] ] –>Links

Comment on:

Evidence and lack of evidence for the initial dip in the anesthetized rat: implications for human functional brain imaging.

Vanzetta I, Grinvald A.

Department of Neurobiology, Weizmann Institute of Science, Rehovot 76100, Israel.

Publication Types:

PMID: 11352602 [PubMed - indexed for MEDLINE]

7: Science. 1999 Nov 19;286(5444):1555-8. Related Articles, var Menu10567261 = [ ["UseLocalConfig", "jsmenu3Config", "", ""], ["Compound (MeSH Keyword)" , "window.top.location='/sites/entrez?Db=pccompound&DbFrom=pubmed&Cmd=Link&LinkName=pubmed_pccompound_mesh&LinkReadableName=Compound%20(MeSH%20Keyword)&IdsFromResult=10567261&ordinalpos=7&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstract' ", "", ""], ["Substance (MeSH Keyword)" , "window.top.location='/sites/entrez?Db=pcsubstance&DbFrom=pubmed&Cmd=Link&LinkName=pubmed_pcsubstance_mesh&LinkReadableName=Substance%20(MeSH%20Keyword)&IdsFromResult=10567261&ordinalpos=7&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstract' ", "", ""], ["Cited in PMC" , "window.top.location='http://www.pubmedcentral.gov/tocrender.fcgi?action=cited&tool=pubmed&pubmedid=10567261&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstract&ordinalpos=7' ", "", ""], ["LinkOut", "window.top.location='/sites/entrez?Cmd=ShowLinkOut&Db=pubmed&TermToSearch=10567261&ordinalpos=7&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstract' ", "", ""] ] –>Links

Increased cortical oxidative metabolism due to sensory stimulation: implications for functional brain imaging.

Vanzetta I, Grinvald A.

Department of Neurobiology, Center for Research of Higher Brain Functions, Weizmann Institute of Science, Rehovot 76100, Israel.

Modern functional brain mapping relies on interactions of neuronal electrical activity with the cortical microcirculation. The existence of a highly localized, stimulus-evoked initial deoxygenation has remained a controversy. Here, the activity-dependent oxygen tension changes in the microcirculation were measured directly, using oxygen-dependent phosphorescence quenching of an exogenous indicator. The first event after sensory stimulation was an increase in oxygen consumption, followed by an increase in blood flow. Because oxygen consumption and neuronal activity are colocalized but the delayed blood flow is not, functional magnetic resonance imaging focused on this initial phase will yield much higher spatial resolution, ultimately enabling the noninvasive visualization of fundamental processing modules in the human brain.

Publication Types:

Research Support, Non-U.S. Gov’t

PMID: 10567261 [PubMed - indexed for MEDLINE]

8: Science. 1996 Apr 26;272(5261):551-4. Related Articles, var Menu8614805 = [ ["UseLocalConfig", "jsmenu3Config", "", ""], ["Substance (MeSH Keyword)" , "window.top.location='/sites/entrez?Db=pcsubstance&DbFrom=pubmed&Cmd=Link&LinkName=pubmed_pcsubstance_mesh&LinkReadableName=Substance%20(MeSH%20Keyword)&IdsFromResult=8614805&ordinalpos=8&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstract' ", "", ""], ["Cited in PMC" , "window.top.location='http://www.pubmedcentral.gov/tocrender.fcgi?action=cited&tool=pubmed&pubmedid=8614805&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstract&ordinalpos=8' ", "", ""], ["LinkOut", "window.top.location='/sites/entrez?Cmd=ShowLinkOut&Db=pubmed&TermToSearch=8614805&ordinalpos=8&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstract' ", "", ""] ] –>Links

Interactions between electrical activity and cortical microcirculation revealed by imaging spectroscopy: implications for functional brain mapping.

Malonek D, Grinvald A.

Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.

Modern neuroimaging techniques use signals originating from microcirculation to map brain function. In this study, activity-dependent changes in oxyhemoglobin, deoxyhemoglobin, and light scattering were characterized by an imaging spectroscopy approach that offers high spatial, temporal, and spectral resolution. Sensory stimulation of cortical columns initiates tissue hypoxia and vascular responses that occur within the first 3 seconds and are highly localized to individual cortical columns. However, the later phase of the vascular response is less localized, spreading over distances of 3 to 5 millimeters.