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The systems-level transcriptional architecture of song plasticity in songbirds

鸣禽鸣叫可塑性的系统级转录结构

基本信息

批准号：
9192887
负责人：
Bradley Mark Colquitt
金额：
$ 5.61万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-07-01 至 2019-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9192887
关键词：
Address Adolescent Adult Animals Anterior Architecture Area Auditory Auditory area Basal Ganglia Behavior Behavioral Birds Brain region Cell Nucleus Complex Cues Dependency Development Environment Event Exhibits Exposure to Finches Gene Expression Gene Expression Profile Gene Expression Profiling Genetic Transcription Genome High-Throughput RNA Sequencing Human Huntington Disease Individual Lasers Learning Lesion Maintenance Mammals Measurable Methodology Methods Modeling Molecular Molecular Models Motor Motor Pathways Motor Skills Motor output Neural Pathways Neurodegenerative Disorders Neurosciences Output Parkinson Disease Pathway interactions Pattern Phase Physiological Play Process Production Property Prosencephalon Role Sampling Sensory Series Signal Transduction Slice Songbirds Speech Structure System Testing Time Tissues Walking Work abstracting auditory feedback base behavior influence behavioral plasticity cost experience instrument learned behavior molecular modeling motor learning motor skill learning nervous system disorder neural circuit neurophysiology prevent psychologic rehearsal relating to nervous system research study response skill acquisition transcriptome sequencing tutoring vocal learning vocalization

项目摘要

Project Summary Abstract Motor skill learning, like learning how to speak, walk, or play a musical instrument, is an essential part of behavioral development. Extensive past work has characterized motor learning at psychological, neurophysiological, and cellular levels. However, there is relatively poorer understanding of how the neural systems that underlie this form of learning change at the molecular level during behavioral plasticity. Moreover, there is little definition of how plasticity within a multi-locus neural system is reflected in coordinated alterations to gene expression. Such a systems-level understanding of the interconnections between behavioral and molecular plasticity is essential to broader understanding of the pathological alterations in neurological disease and the molecular conditions that promote or constrain plasticity. In particular, song learning is highly analogous to speech learning in humans and to general motor skill acquisition, exhibiting similar behavioral trajectories and employing homologous neural systems. Disruptions to these neural systems in humans are strongly associated with motor-associated neurodegenerative disease such as Parkinson's and Huntington's diseases. This proposal will use song learning in songbirds, a tractable and ethologically relevant model of motor skill learning with highly controllable inputs, precisely measurable outputs, and defined neural substrates, to characterize the transcriptional states that underlie motor skill acquisition and destabilization. The broad, long-term objective of this work is to understand the molecular mechanisms that contribute to plasticity in a complex learned behavior, both during normal development and during pathological disruption. This proposal will focus on two specific hypotheses. The first aim will test the hypothesis that song acquisition in juveniles induces specific transcriptional responses in the song system. Moreover, this aim will test the hypothesis that initial tutor song exposure and subsequent song learning induce distinct transcriptional states. The second aim will test the hypothesis that deafening in adult birds, a manipulation that drives song destabilization, drives transcriptional responses in the song system. Past work has demonstrated that deafening-induced song destabilization requires intact signaling from the cortical-basal ganglia system that underlies song learning. Following from this result, this aim will also test the hypothesis that this dependency extends to the level of gene expression by examining transcriptional responses in the song system in deafened birds that lack intact cortical-basal ganglia output to the song motor pathway. To enable this work, we have developed a low-cost and high-throughput RNA sequencing method that permits the analysis of gene expression in hundreds of individual laser microdissected samples from single animals. Together, these experiments will establish a framework for understanding the molecular basis of alterations in complex behaviors.

项目摘要