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Birdsong "transcriptomics": neurochemical specializations of the oscine song system.

Lovell PV, Clayton DF, Replogle KL, Mello CV - PLoS ONE (2008)

Bottom Line: These markers clearly differentiate HVC from the general pallial region to which HVC belongs, and thus represent molecular specializations of this song nucleus.Our study represents one of the most comprehensive molecular genetic characterizations of a brain nucleus involved in a complex learned behavior in a vertebrate.The data indicate numerous targets for pharmacological and genetic manipulations of the song system, and provide novel insights into mechanisms that might play a role in the regulation of song behavior and/or vocal learning.

View Article: PubMed Central - PubMed

Affiliation: Neurological Sciences Institute, Oregon Health and Science University, Beaverton, Oregon, United States of America.

ABSTRACT

Background: Vocal learning is a rare and complex behavioral trait that serves as a basis for the acquisition of human spoken language. In songbirds, vocal learning and production depend on a set of specialized brain nuclei known as the song system.

Methodology/principal findings: Using high-throughput functional genomics we have identified approximately 200 novel molecular markers of adult zebra finch HVC, a key node of the song system. These markers clearly differentiate HVC from the general pallial region to which HVC belongs, and thus represent molecular specializations of this song nucleus. Bioinformatics analysis reveals that several major neuronal cell functions and specific biochemical pathways are the targets of transcriptional regulation in HVC, including: 1) cell-cell and cell-substrate interactions (e.g., cadherin/catenin-mediated adherens junctions, collagen-mediated focal adhesions, and semaphorin-neuropilin/plexin axon guidance pathways); 2) cell excitability (e.g., potassium channel subfamilies, cholinergic and serotonergic receptors, neuropeptides and neuropeptide receptors); 3) signal transduction (e.g., calcium regulatory proteins, regulators of G-protein-related signaling); 4) cell proliferation/death, migration and differentiation (e.g., TGF-beta/BMP and p53 pathways); and 5) regulation of gene expression (candidate retinoid and steroid targets, modulators of chromatin/nucleolar organization). The overall direction of regulation suggest that processes related to cell stability are enhanced, whereas proliferation, growth and plasticity are largely suppressed in adult HVC, consistent with the observation that song in this songbird species is mostly stable in adulthood.

Conclusions/significance: Our study represents one of the most comprehensive molecular genetic characterizations of a brain nucleus involved in a complex learned behavior in a vertebrate. The data indicate numerous targets for pharmacological and genetic manipulations of the song system, and provide novel insights into mechanisms that might play a role in the regulation of song behavior and/or vocal learning.

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(A–D) Representative in situ hybridization autoradiograms of parasagittal sections of adult male zebra finches at the level of HVC (∼1.4 to 2.4 mm from the midline).(A, left) Schematic depicting the major telencephalic song nuclei (in black), thalamorecipient areas (i.e. L2a, Bas), and major brain subdivisions. (A, center and right) Expression of known HVC markers. The other panels (B–D) depict representative autoradiograms of HVC markers that are exclusive to HVC (B), enriched in HVC and other song nuclei, such as LMAN (C, left), or area X (C, center and right; inset shows area X from a more medial section), enriched in 3/4 major song nuclei (D, left and middle), or are negative markers (D, right). Notice that some markers are also enriched in distinct pallial and striatal areas, and/or primary sensory areas. Scalebar: 1 mm. Gene abbreviations in Table S1. Anatomical abbreviations: A, Arcopallium; Bas, nucleus basorostralis; Cb, Cerebellum; GP, globus pallidus; Hp; Hippocampus; H, Hyperpallium; L2a, subfield L2a of field L; LMAN, lateral magnocellular nucleus of the anterior nidopallium; M, Mesopallium; N, Nidopallium; RA, robust nucleus of the arcopallium; Ot, optic tract; Rt, nucleus rotundus; St; striatum.
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pone-0003440-g002: (A–D) Representative in situ hybridization autoradiograms of parasagittal sections of adult male zebra finches at the level of HVC (∼1.4 to 2.4 mm from the midline).(A, left) Schematic depicting the major telencephalic song nuclei (in black), thalamorecipient areas (i.e. L2a, Bas), and major brain subdivisions. (A, center and right) Expression of known HVC markers. The other panels (B–D) depict representative autoradiograms of HVC markers that are exclusive to HVC (B), enriched in HVC and other song nuclei, such as LMAN (C, left), or area X (C, center and right; inset shows area X from a more medial section), enriched in 3/4 major song nuclei (D, left and middle), or are negative markers (D, right). Notice that some markers are also enriched in distinct pallial and striatal areas, and/or primary sensory areas. Scalebar: 1 mm. Gene abbreviations in Table S1. Anatomical abbreviations: A, Arcopallium; Bas, nucleus basorostralis; Cb, Cerebellum; GP, globus pallidus; Hp; Hippocampus; H, Hyperpallium; L2a, subfield L2a of field L; LMAN, lateral magnocellular nucleus of the anterior nidopallium; M, Mesopallium; N, Nidopallium; RA, robust nucleus of the arcopallium; Ot, optic tract; Rt, nucleus rotundus; St; striatum.

Mentions: Providing further validation for our screening, many known HVC markers were present on our primary (n = 11) and secondary (n = 13) lists (presented in Table S3). Among these, retinaldehyde dehydrogenase (zRalDH; Fig. 2A, middle; [24]), Calmodulin-binding transcription activator 1 [25], Neurofilament triplet light and medium ([26]; see Fig. 2A, right), Phantom2 [27], insulin-like growth factor 2 [28], voltage-gated potassium channel subfamily C3 (Velho and Mello, unpublished observation), a metabotropic glutamate receptor (GRM8; [25]), the gene deleted in bladder cancer (DBC1, a.k.a. brinp1; [29]), and Parvalbumin [30] were all confirmed to be enriched in HVC, whereas P450 aromatase [31], [32], several glutamate receptors subunits (GRIA2, GRIA3, GRIA4, GRIK2, GRM1, and GRM5; [33]), N-chimaerin [34], alpha-synuclein [35], Reelin isoform A [25] and hydroxysteroid (17-beta) dehydrogenase 11/13 ([29]) were all confirmed to have lower expression in HVC, and several glutamate receptor subunits were confirmed as not differential (GRM3, GRIK3, GRIN1; Table S3).


Birdsong "transcriptomics": neurochemical specializations of the oscine song system.

Lovell PV, Clayton DF, Replogle KL, Mello CV - PLoS ONE (2008)

(A–D) Representative in situ hybridization autoradiograms of parasagittal sections of adult male zebra finches at the level of HVC (∼1.4 to 2.4 mm from the midline).(A, left) Schematic depicting the major telencephalic song nuclei (in black), thalamorecipient areas (i.e. L2a, Bas), and major brain subdivisions. (A, center and right) Expression of known HVC markers. The other panels (B–D) depict representative autoradiograms of HVC markers that are exclusive to HVC (B), enriched in HVC and other song nuclei, such as LMAN (C, left), or area X (C, center and right; inset shows area X from a more medial section), enriched in 3/4 major song nuclei (D, left and middle), or are negative markers (D, right). Notice that some markers are also enriched in distinct pallial and striatal areas, and/or primary sensory areas. Scalebar: 1 mm. Gene abbreviations in Table S1. Anatomical abbreviations: A, Arcopallium; Bas, nucleus basorostralis; Cb, Cerebellum; GP, globus pallidus; Hp; Hippocampus; H, Hyperpallium; L2a, subfield L2a of field L; LMAN, lateral magnocellular nucleus of the anterior nidopallium; M, Mesopallium; N, Nidopallium; RA, robust nucleus of the arcopallium; Ot, optic tract; Rt, nucleus rotundus; St; striatum.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2563692&req=5

pone-0003440-g002: (A–D) Representative in situ hybridization autoradiograms of parasagittal sections of adult male zebra finches at the level of HVC (∼1.4 to 2.4 mm from the midline).(A, left) Schematic depicting the major telencephalic song nuclei (in black), thalamorecipient areas (i.e. L2a, Bas), and major brain subdivisions. (A, center and right) Expression of known HVC markers. The other panels (B–D) depict representative autoradiograms of HVC markers that are exclusive to HVC (B), enriched in HVC and other song nuclei, such as LMAN (C, left), or area X (C, center and right; inset shows area X from a more medial section), enriched in 3/4 major song nuclei (D, left and middle), or are negative markers (D, right). Notice that some markers are also enriched in distinct pallial and striatal areas, and/or primary sensory areas. Scalebar: 1 mm. Gene abbreviations in Table S1. Anatomical abbreviations: A, Arcopallium; Bas, nucleus basorostralis; Cb, Cerebellum; GP, globus pallidus; Hp; Hippocampus; H, Hyperpallium; L2a, subfield L2a of field L; LMAN, lateral magnocellular nucleus of the anterior nidopallium; M, Mesopallium; N, Nidopallium; RA, robust nucleus of the arcopallium; Ot, optic tract; Rt, nucleus rotundus; St; striatum.
Mentions: Providing further validation for our screening, many known HVC markers were present on our primary (n = 11) and secondary (n = 13) lists (presented in Table S3). Among these, retinaldehyde dehydrogenase (zRalDH; Fig. 2A, middle; [24]), Calmodulin-binding transcription activator 1 [25], Neurofilament triplet light and medium ([26]; see Fig. 2A, right), Phantom2 [27], insulin-like growth factor 2 [28], voltage-gated potassium channel subfamily C3 (Velho and Mello, unpublished observation), a metabotropic glutamate receptor (GRM8; [25]), the gene deleted in bladder cancer (DBC1, a.k.a. brinp1; [29]), and Parvalbumin [30] were all confirmed to be enriched in HVC, whereas P450 aromatase [31], [32], several glutamate receptors subunits (GRIA2, GRIA3, GRIA4, GRIK2, GRM1, and GRM5; [33]), N-chimaerin [34], alpha-synuclein [35], Reelin isoform A [25] and hydroxysteroid (17-beta) dehydrogenase 11/13 ([29]) were all confirmed to have lower expression in HVC, and several glutamate receptor subunits were confirmed as not differential (GRM3, GRIK3, GRIN1; Table S3).

Bottom Line: These markers clearly differentiate HVC from the general pallial region to which HVC belongs, and thus represent molecular specializations of this song nucleus.Our study represents one of the most comprehensive molecular genetic characterizations of a brain nucleus involved in a complex learned behavior in a vertebrate.The data indicate numerous targets for pharmacological and genetic manipulations of the song system, and provide novel insights into mechanisms that might play a role in the regulation of song behavior and/or vocal learning.

View Article: PubMed Central - PubMed

Affiliation: Neurological Sciences Institute, Oregon Health and Science University, Beaverton, Oregon, United States of America.

ABSTRACT

Background: Vocal learning is a rare and complex behavioral trait that serves as a basis for the acquisition of human spoken language. In songbirds, vocal learning and production depend on a set of specialized brain nuclei known as the song system.

Methodology/principal findings: Using high-throughput functional genomics we have identified approximately 200 novel molecular markers of adult zebra finch HVC, a key node of the song system. These markers clearly differentiate HVC from the general pallial region to which HVC belongs, and thus represent molecular specializations of this song nucleus. Bioinformatics analysis reveals that several major neuronal cell functions and specific biochemical pathways are the targets of transcriptional regulation in HVC, including: 1) cell-cell and cell-substrate interactions (e.g., cadherin/catenin-mediated adherens junctions, collagen-mediated focal adhesions, and semaphorin-neuropilin/plexin axon guidance pathways); 2) cell excitability (e.g., potassium channel subfamilies, cholinergic and serotonergic receptors, neuropeptides and neuropeptide receptors); 3) signal transduction (e.g., calcium regulatory proteins, regulators of G-protein-related signaling); 4) cell proliferation/death, migration and differentiation (e.g., TGF-beta/BMP and p53 pathways); and 5) regulation of gene expression (candidate retinoid and steroid targets, modulators of chromatin/nucleolar organization). The overall direction of regulation suggest that processes related to cell stability are enhanced, whereas proliferation, growth and plasticity are largely suppressed in adult HVC, consistent with the observation that song in this songbird species is mostly stable in adulthood.

Conclusions/significance: Our study represents one of the most comprehensive molecular genetic characterizations of a brain nucleus involved in a complex learned behavior in a vertebrate. The data indicate numerous targets for pharmacological and genetic manipulations of the song system, and provide novel insights into mechanisms that might play a role in the regulation of song behavior and/or vocal learning.

Show MeSH
Related in: MedlinePlus