Learning-induced changes in distinct auditory cortical cell-types

项目摘要 当听觉信息被用来驱动我们的决策和行动时，听觉引导的行为就会发生。的 听觉皮层（ACtx）位于上行听觉通路的顶端，但将声学特征转化为 行为结果需要与该听觉层级之外的区域进行通信。主 ACtx在整个大脑中传播听觉信息的途径是通过端脑内（IT）， 皮质层（L）5中的端脑外（ET）神经元，其基于它们的不同和大部分分类。 不重叠的投影目标。然而，很少有人知道这些不同的功能差异， ACtx内的兴奋性群体。研究大脑引导行为的神经回路以及如何 听觉信息被用来驱动行为将填补我们知识中的一个重大空白。无处不在的听觉- 引导行为是分类：将声学特征转换为离散的感知类别， 驱动后续的行为结果。为了研究L5 IT和ET神经元在这种行为中的作用，我们 为小鼠设计了一种新的听觉分类任务，并在几天内进行了双光子成像， 学习我们的初步数据表明，L5 IT和ET神经元在其表达上表现出分歧， 刺激类别和行为选择，这是雕刻在学习。这表明，IT预测是 教育技术预测在学习的初始阶段很重要，而教育技术预测则在整个学习过程中得到招募和加强。 目标1将确定L5 IT和ET神经元对学习听觉分类任务的贡献， 目标2将检查这些神经元是否在学习过程中对行为选择进行差异编码。结合起来，这些 两个具体的目标将提供初步的见解，如何两个不同的兴奋性细胞类型在最大的皮层输出 层有助于由知识引导行为。这些实验的结果将扩展我们对 感觉信息如何在大脑中传播以及皮层回路如何使复杂的 行为。此外，这项建议将大大提高我的个人和专业发展， 独立的科学家。成功地完成这份提案将为我的长期目标做好准备， 成为听觉神经科学的首席研究员

PROJECT SUMMARY Auditory-guided behaviors occur whenever auditory information is used to drive our decisions and actions. The auditory cortex (ACtx) sits at the apex of the ascending auditory pathway but transforming acoustic features into a behavioral outcome necessitates communication with regions outside of this auditory hierarchy. The primary routes for ACtx to propagate auditory information throughout the brain are through intratelencephalic (IT) and extratelencephalic (ET) neurons in cortical layer (L) 5, which are classified based on their distinct and largely non-overlapping projection targets. However, little is known about the functional differences of these distinct excitatory populations within ACtx. Investigating the neural circuitry underlying auditory-guided behavior and how auditory information is used to drive behavior would fill a significant gap in our knowledge. A ubiquitous auditory- guided behavior is categorization: the transformation of acoustic features into discrete perceptual categories that drive a subsequent behavioral outcome. To investigate the role of L5 IT and ET neurons in such a behavior, we designed a novel auditory categorization task for mice and performed two-photon imaging across days of learning. Our preliminary data shows that L5 IT and ET neurons exhibit a divergence in their representation of stimulus category and behavioral choice that is sculpted across learning. This suggests that IT projections are important in initial stages of learning while ET projections are recruited and strengthened throughout learning. Aim 1 will determine the contributions of L5 IT and ET neurons to learning an auditory categorization task and Aim 2 will examine if these neurons differentially encode behavioral choice across learning. Combined, these two Specific Aims will provide initial insight as to how two distinct excitatory cell-types in the largest cortical output layer contribute to auditory-guided behavior. The outcomes of these experiments will expand our understanding of how sensory information is propagated throughout the brain and how cortical circuits enable complex behaviors. Furthermore, this proposal will considerably enhance my personal and professional development as an independent scientist. Successful completion of this proposal will prepare me for my long-term goal of becoming a principal investigator in auditory neuroscience.