Project description:A defining feature of our species is the ability to manipulate our environment through the fine control of our hands and to communicate with others through the rapid and complex motor orchestration of human speech. The courtship song of songbirds shares a number of neural and behavioral similarities with human speech and other learned motor skills, providing a powerful model for understanding how enhanced motor skills develop at molecular and cellular levels. Birdsong is controlled by a specialized neural circuit whose properties enable high precision and speed. In particular, glutamatergic neurons in the birdsong motor region RA (Glut-RA) have higher spike rates and narrower action potentials than projection neurons in an adjacent motor region that does not control song, the dorsal intermediate arcopallium (Glut-AId). To identify candidate gene regulatory networks that establish the specialized properties of Glut-RA neurons, we performed single-nucleus profiling of gene expression and chromatin accessibility across song and non-song motor regions. We found that Glut-RA projection neurons and fast spiking interneurons (FSIs), a GABAergic type also characterized by high spike rates and narrow action potentials, share several transcriptional similarities. In particular, the transcription factor MAFB, which is essential for the development and fast-spiking physiology of FSIs in mice, is expressed in Glut-RA but no other projection neuron type. We found that MAFB transcription factor binding sites have enhanced chromatin accessibility specifically in glutamatergic neurons in RA relative to AId. Furthermore, gene regulatory network inference and in silico knockdown of MAFB expression reveal common MAFB targets in Glut-RA neurons and FSIs, and suggest that the transcription factor is necessary to specialize song Glut-RA neurons from non-song Glut-AId neurons. These data support a model in which birdsong projection neurons co-opt an interneuron gene regulatory program to enable the rapid physiological properties required for fast and precise birdsong performance.

			Action	DRS
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	SRR18732327.fastq.gz	Fastqsanger.gz

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Analysis of the effects of deafening on gene expression in birdsong neural circuitry

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