Learning-induced changes in distinct auditory cortical cell-types

学习引起的不同听觉皮层细胞类型的变化

• 批准号: 10823770
• 负责人: Nathan A Schneider
• 金额: $ 4.77万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10823770
• 关键词: Acoustics; Animals; Apical; Auditory; Auditory area; Behavior; Behavior Disorders; Behavioral; Brain; Calcium; Categories; Classification; Code; Cognition Disorders; Communication; Complex; Comprehension; Data; Decision Making; Development; Exhibits; Foundations; Goals; Head; Human; Image; Information Theory; Knowledge; Learning; Left; Monitor; Motor; Mus; Neurons; Neurosciences; Outcome; Output; Pattern; Performance; Phase; Population; Positioning Attribute; Principal Investigator; Process; Property; Reporting; Rewards; Role; Route; Scientist; Sensory; Shapes; Speech; Stimulus; Structure; Time; association cortex; auditory categorization; auditory pathway; auditory stimulus; behavioral outcome; cell type; design; excitatory neuron; experimental study; frontal lobe; information processing; insight; neural; neural circuit; novel; optogenetics; recruit; response; serial imaging; sound; two-photon

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.

项目概要 每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。这 听觉皮层 (ACtx) 位于上行听觉通路的顶点，但将声学特征转化为 行为结果需要与听觉层次之外的区域进行交流。初级 ACtx 在整个大脑中传播听觉信息的途径是通过端脑内 (IT) 和 皮质层 (L) 5 中的端脑外 (ET) 神经元根据其独特性和很大程度上进行分类 不重叠的投影目标。然而，人们对这些不同的功能差异知之甚少。 ACtx 内的兴奋性群体。研究听觉引导行为背后的神经回路以及如何 听觉信息用于驱动行为将填补我们知识的重大空白。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颖的听觉分类任务，并在数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 神经元在表征方面表现出差异 在学习中塑造的刺激类别和行为选择。这表明 IT 预测是 在学习的初始阶段很重要，而 ET 预测在整个学习过程中都会被招募和加强。 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，以及 目标 2 将检查这些神经元是否对学习过程中的行为选择进行差异编码。综合起来，这些 两个具体目标将提供关于两种不同的兴奋性细胞类型如何在最大皮质输出中的初步见解 层有助于听觉引导行为。这些实验的结果将扩大我们的理解 感觉信息如何在整个大脑中传播以及皮层回路如何实现复杂的 行为。此外，这项建议将极大地促进我的个人和职业发展 一位独立科学家。成功完成该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。