Developmental changes in neural circuits for a behavior

描述（由申请人提供）：动物在有限的发育期内与外部世界的相互作用对其行为能力具有深远而持久的影响。虽然感官经验在习得行为发展中的作用已经得到了很好的确立，但经验塑造这些行为背后的神经回路的机制还没有得到很好的理解。鸣禽和人类一样，在特定的发育时期听到它们的声音后，学习它们的物种典型的发声，并且发声行为由高度局部化的神经回路控制。我们将使用鸣禽模型系统来研究内源性和经验性因素如何调节神经和行为发育。(1)我们将研究神经营养因子（一种特定的生长因子）在控制发声学习的神经回路中表达的发育变化，以产生有关其作用位点和机制的假设。(2)我们将测试是否释放神经营养因子从轴突末梢的活性神经元可以调节其突触后靶神经元的存活和/或分化。(3)我们将研究发声控制回路的电生理学，重点是神经营养生长因子调节兴奋性突触传递的发育变化，以表征神经元之间的功能性通信模式。(4)我们将研究在发声发育过程中单个神经元轴突终末的形态，以评估发声控制神经回路之间连接的特异性，并研究听觉剥夺对单个轴突发育造成的发声学习中断的影响。(5)我们将评估神经营养因子对单个轴突终末发育的影响，以此作为一种手段来测试如何在发育早期的受限敏感期内，在声音控制神经回路中高度有序的连接模式及其所支持的专门行为。

DESCRIPTION (provided by applicant): An animal's interactions with its external world during restricted periods of development have a profound and lasting influence on its behavioral capacities. Although the role of sensory experience in the development of learned behaviors is well established, the mechanisms whereby experience shapes neural circuits underlying such behaviors are not well understood. Songbirds, like humans, learn their species-typical vocalizations after hearing them during a specific period of development, and vocal behavior is controlled by highly localized neural circuits. We will use the songbird model system to investigate how endogenous and experiential factors regulate neural and behavioral development. (1) We will examine developmental changes in the expression of neurotrophins, a specific class of growth factors, in neural circuits that control vocal learning in order to generate hypotheses concerning their locus and mechanism of action. (2) We will test whether release of neurotrophins from axon terminals of active neurons can regulate the survival and/or differentiation of their post-synaptic target neurons. (3) We will investigate the electrophysiology of vocal-control circuits, focusing on developmental changes in regulation of excitatory synaptic transmission by neurotrophin growth factors in order to characterize patterns of functional communication between neurons. (4) We will study the morphology of axon terminals of individual neurons during vocal development to assess the specificity of connections among vocal-control neural circuits, and examine the influence of disruptions in vocal learning due to auditory deprivation on development of single axons. (5) We will assess the influence of neurotrophins on the development of individual axon terminals as a means of testing how highly ordered patterns of connectivity within vocal-control neural circuits and the specialized behaviors they subserve emerge during restricted sensitive periods early in development.