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.

项目概要 将感官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 对于健康和疾病，我们对于如何赋予感官刺激意义以及如何使用感官刺激来知之甚少。 引导行为。背侧纹状体被认为对于感觉运动的形成特别重要 强化学习过程中由于接收到的多巴胺能输入以及多种因素而产生的关联 皮质和皮质下输入的数组。有两种细胞类型构成了两条输出途径 背侧纹状体、直接通路纹状体投射神经元 (dSPN) 和间接通路纹状体神经元 （iSPN）。虽然很多工作都集中在这些途径如何发挥作用来启动运动，但很少有研究 了解感觉学习如何影响这些神经元的神经元活动以及这会产生什么影响 行为上。 构成该提案的实验提供了一个框架，用于理解感官输入如何 塑造背侧纹状体中 dSPN 和 iSPN 的活动。在本提案中，我们重点关注以下具体部分： 背侧纹状体称为听觉纹状体（AudStr），接收密集的听觉输入。我们 假设听觉感觉运动学习能够形成与相关的线索特定的整体 并预测电机输出。我们预计这些变化将主要由突触可塑性驱动 输入收敛到 SPN，而不是改变其内在兴奋性。 我们将执行两个独立且相互关联的目标来检验这一假设。我们将训练小鼠完成一项任务 这要求他们将“开始”提示与特定的动作联系起来以获得奖励，并抑制这种行为 响应“禁止”提示而采取的行动。在目标 1 中，我们将采用 AudStr 神经元的纵向钙成像来 表征这些神经元在学习之前和之后的输出线索。在目标 2 中，我们将探索 学习导致的群体活动预期变化背后的细胞机制，旨在 证明 AudStr 中突触可塑性对此过程的重要性。为了实现这两个目标，我们将采用 使我们能够将神经元识别为 dSPN 和 iSPN 的方法。这一点至关重要，因为一个主要的突出 该领域的问题是这些细胞类型在产生适当的细胞因子方面是否发挥相反或互补的作用 运动反应。总的来说，这项工作将为理解的新概念模型奠定基础 感觉学习如何影响纹状体活动以控制行为。