Sensory Plasticity in the Auditory Striatum as an Impetus for Action Control

听觉纹状体的感觉可塑性作为行动控制的动力

• 批准号: 10576948
• 负责人: Tanya Sippy
• 金额: $ 47.83万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-03-01 至 2027-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10576948
• 关键词: Address; Animals; Auditory; Basal Ganglia; Behavior; Behavior Control; Behavioral; Brain; Brain region; Calcium; Cells; Corpus striatum structure; Cues; Development; Disease; Dorsal; Ganglia; Goals; Health; Image; Learning; Link; Maps; Measures; Membrane Potentials; Methods; Modeling; Motor; Motor Activity; Motor output; Movement; Mus; Neurons; Output; Pathway interactions; Pattern; Play; Population; Population Dynamics; Process; Property; Psychological reinforcement; Rewards; Role; Sensory; Shapes; Site; Specific qualifier value; Synapses; Synaptic plasticity; Testing; Time; Training; Transgenic Organisms; Translating; Whole-Cell Recordings; Work; auditory discrimination; cell type; experience; experimental study; in vivo; motor behavior; motor control; neural; neuromechanism; predictive modeling; recruit; response; sensory input; sensory stimulus; two-photon

Project Summary The ability to translate sensory experiences into action is essential for our survival. Despite its importance in health and disease, we know remarkably little about how we assign meaning to and use sensory stimuli to guide behavior. The dorsal striatum is thought to be particularly important for the formation of sensorimotor associations during reinforcement learning due to the dopaminergic inputs it receives, as well as a diverse array of cortical and subcortical inputs. There are two cell types that make up the two output pathways of the dorsal striatum, direct pathway striatal projection neurons (dSPNs) and indirect pathway striatal neurons (iSPNs). While much work has focused on how these pathways might function to initiate movements, very little is known about how sensory learning influences the neuronal activity of these neurons and what effect this has on behavior. The experiments that make up this proposal provide a framework for understanding how sensory input shapes the activity of dSPNs and iSPNs in the dorsal striatum. In this proposal, we focus on a specific part of the dorsal striatum known as the auditory striatum (AudStr), that receives dense auditory inputs. We hypothesize that auditory sensorimotor learning enables the formation of cue-specific ensembles that correlate with and predict motor output. We expect that these changes will be primarily driven by synaptic plasticity of inputs that converge onto SPNs, rather than changes to their intrinsic excitability. We will perform two independent, inter-related aims to test this hypothesis. We will train mice on a task that requires them to associate a 'go' cue with a specified action to receive a reward, and to suppress this action in response to a 'no-go' cue. In Aim 1, we will employ longitudinal calcium imaging of AudStr neurons to characterize the outputs of these neurons to cues before and after learning. In Aim 2, we will explore the cellular mechanisms underlying anticipated changes in population activity that results from learning, and aim to demonstrate the importance of synaptic plasticity in the AudStr to this process. In both aims we will employ methods that enable us to identify neurons as dSPNs and iSPNs. This is crucial because a major outstanding question in this field is whether these cell types play opposing or complementary roles in producing appropriate motor responses. Overall, this work will lay the groundwork for a new conceptual model for understanding how sensory learning influences striatal activity to control behavior.

项目摘要 将感觉体验转化为行动的能力对于我们的生存至关重要。尽管它的重要性 健康和疾病，我们对如何将意义分配给和使用感官刺激分配给 指南行为。据认为，背纹状体对于感觉运动尤其重要 由于收到的多巴胺能输入而引起的加固学习过程中的关联，以及多样的 皮质和皮层输入的阵列。有两种构成了两种输出途径的单元格类型 背纹状体，直接途径纹状体投影神经元（DSPN）和间接途径纹状体神经元 （ISPN）。尽管很多工作集中在这些途径如何发挥运动时，但很少 知道感觉学习如何影响这些神经元的神经元活性以及这有什么影响 关于行为。 构成该建议的实验提供了一个框架，以了解感官输入的方式 塑造背侧纹状体中DSPN和ISPN的活性。在此提案中，我们专注于 接收致密听觉输入的后背纹状体称为听觉纹状体（AUDSTR）。我们 假设听觉感觉运动学习能够形成相关的提示特异性集合 并预测电动机输出。我们希望这些变化主要由 收敛到SPN的输入，而不是改变其内在兴奋性。 我们将执行两个独立的相互关联目的来检验这一假设。我们将训练老鼠完成一项任务 这要求他们将“ GO”提示与指定的行动相关联，以获得奖励，并压制这一点 响应“无关”提示的行动。在AIM 1中，我们将使用Audstr神经元的纵钙成像到 在学习前后，将这些神经元的输出表征为提示。在AIM 2中，我们将探索 细胞机制是由学习导致的预期人群活动变化的，旨在 证明突触可塑性在AUDSTR中对此过程的重要性。在这两个目标中，我们都将采用 使我们能够将神经元识别为DSPN和ISPN的方法。这是至关重要的 该领域的问题是这些细胞类型在生产适当的 电机响应。总体而言，这项工作将为理解新的概念模型奠定基础 感觉学习如何影响纹状体活动以控制行为。