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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–C) Bright-field high power Nissl stained views of NRP1 emulsion autoradiography at the level of HVC. Black arrowheads indicate examples of small cells with high levels of emulsion grains (A), white arrows point to larger neurons with no detectable expression (see also C). (D) Low power dark-field autoradiography for SEMA3A in a parasagittal section at the level of RA. Note intensely labeled cells that align along the lamina arcopallius dorsalis (LAD). (E) Camera lucida drawing of the ventral nidopallium and arcopallium from the section shown in D. Individual cells expressing SEMA3A are represented by solid circles. For anatomical abbreviations see text. Scalebars: 10 µm in A–C; 100 µM in D; 1 mm in E.
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pone-0003440-g005: (A–C) Bright-field high power Nissl stained views of NRP1 emulsion autoradiography at the level of HVC. Black arrowheads indicate examples of small cells with high levels of emulsion grains (A), white arrows point to larger neurons with no detectable expression (see also C). (D) Low power dark-field autoradiography for SEMA3A in a parasagittal section at the level of RA. Note intensely labeled cells that align along the lamina arcopallius dorsalis (LAD). (E) Camera lucida drawing of the ventral nidopallium and arcopallium from the section shown in D. Individual cells expressing SEMA3A are represented by solid circles. For anatomical abbreviations see text. Scalebars: 10 µm in A–C; 100 µM in D; 1 mm in E.

Mentions: A significant cluster has been linked to axonal guidance. This included the upregulated neuropilin (NRP1) and plexin-A4 (PLXNA4), which together comprise the receptor for semaphorins 3A and 6A (SEMA3A and SEMA6A), and a PDZ-domain containing ring-finger protein (PDZRN3) that interacts with semaphorins, as well as the downregulated PLXNA1, PLXNB1* (PLXNA2 was not differential), and UNC5C, the latter a receptor for netrins, which are non-semaphorin mediators of axonal guidance (other plexins and semaphorins were not differential). In situ hybridization confirmed that both NRP1 and PLXNA4 are enriched in HVC, and revealed that NRP1 is primarily expressed in clusters of small (Fig. 5A–B), but not large (Fig. 5C) HVC neurons that resemble either RA-projecting cells or interneurons [37]. In contrast, the ligand SEMA3A was confirmed downregulated in HVC and its targets RA and area X (not shown), but was highly enriched in a band of large cells adjacent to the dorsal arcopallial lamina and intercalated with nidopallial axonal bundles entering the arcopallium (Fig. 5D and E).


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

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

(A–C) Bright-field high power Nissl stained views of NRP1 emulsion autoradiography at the level of HVC. Black arrowheads indicate examples of small cells with high levels of emulsion grains (A), white arrows point to larger neurons with no detectable expression (see also C). (D) Low power dark-field autoradiography for SEMA3A in a parasagittal section at the level of RA. Note intensely labeled cells that align along the lamina arcopallius dorsalis (LAD). (E) Camera lucida drawing of the ventral nidopallium and arcopallium from the section shown in D. Individual cells expressing SEMA3A are represented by solid circles. For anatomical abbreviations see text. Scalebars: 10 µm in A–C; 100 µM in D; 1 mm in E.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2563692&req=5

pone-0003440-g005: (A–C) Bright-field high power Nissl stained views of NRP1 emulsion autoradiography at the level of HVC. Black arrowheads indicate examples of small cells with high levels of emulsion grains (A), white arrows point to larger neurons with no detectable expression (see also C). (D) Low power dark-field autoradiography for SEMA3A in a parasagittal section at the level of RA. Note intensely labeled cells that align along the lamina arcopallius dorsalis (LAD). (E) Camera lucida drawing of the ventral nidopallium and arcopallium from the section shown in D. Individual cells expressing SEMA3A are represented by solid circles. For anatomical abbreviations see text. Scalebars: 10 µm in A–C; 100 µM in D; 1 mm in E.
Mentions: A significant cluster has been linked to axonal guidance. This included the upregulated neuropilin (NRP1) and plexin-A4 (PLXNA4), which together comprise the receptor for semaphorins 3A and 6A (SEMA3A and SEMA6A), and a PDZ-domain containing ring-finger protein (PDZRN3) that interacts with semaphorins, as well as the downregulated PLXNA1, PLXNB1* (PLXNA2 was not differential), and UNC5C, the latter a receptor for netrins, which are non-semaphorin mediators of axonal guidance (other plexins and semaphorins were not differential). In situ hybridization confirmed that both NRP1 and PLXNA4 are enriched in HVC, and revealed that NRP1 is primarily expressed in clusters of small (Fig. 5A–B), but not large (Fig. 5C) HVC neurons that resemble either RA-projecting cells or interneurons [37]. In contrast, the ligand SEMA3A was confirmed downregulated in HVC and its targets RA and area X (not shown), but was highly enriched in a band of large cells adjacent to the dorsal arcopallial lamina and intercalated with nidopallial axonal bundles entering the arcopallium (Fig. 5D and E).

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