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.

项目总结 每当听觉信息被用来驱动我们的决定和行动时，就会发生听觉引导的行为。这个 听觉皮质(ACTx)位于上升听觉通路的顶端，但将声学特征转化为 行为结果需要与这个听觉层次结构之外的区域进行交流。初级阶段 ACTx在整个大脑中传播听觉信息的途径是通过脑内(IT)和 皮质层中的脑外(ET)神经元(L)5，根据其明显的和较大的 非重叠投影目标。然而，人们对这些截然不同的基因的功能差异知之甚少。 ACTx内的兴奋性种群。研究听觉引导行为背后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。一种无处不在的听觉- 引导行为是分类：将声学特征转换为离散的感知类别， 推动随后的行为结果。为了研究L5IT和ET神经元在这种行为中的作用，我们 设计了一种新的小鼠听觉分类任务，并在几天的时间里进行了双光子成像 学习。我们的初步数据显示，L5IT和ET神经元在它们的表达方式上表现出分歧 刺激类别和行为选择是通过学习塑造的。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被招募和加强。 目标1将确定L5IT和ET神经元在学习听觉分类任务中的贡献 目标2将研究这些神经元是否在学习过程中编码不同的行为选择。加在一起，这些 两个特定的目标将提供关于两种不同类型的兴奋细胞如何在最大皮层输出中的初步洞察 这一层有助于听觉引导的行为。这些实验的结果将扩大我们的理解 感觉信息是如何在大脑中传播的，以及大脑皮层回路如何使复杂的 行为。此外，这项建议将极大地促进我的个人和职业发展，因为 一个独立的科学家。成功完成这项提议将为我的长期目标做好准备 成为听神经科学的首席研究员。