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

项目摘要 将感官体验转化为行动的能力对我们的生存至关重要。尽管它在 健康和疾病，我们对如何赋予意义并使用感觉刺激来 引导行为。背侧纹状体被认为对感觉运动的形成特别重要。 强化学习期间的联系，由于它接收到的多巴胺能输入，以及不同的 皮质和皮质下输入的数组。有两种单元格类型组成了 背侧纹状体、直接通道纹状体投射神经元和间接通道纹状体神经元 (ISPN)。虽然许多研究都集中在这些通路如何发挥作用来启动运动，但很少有 已知感觉学习如何影响这些神经元的神经元活动，以及这种影响是什么 在行为上。 组成这一建议的实验提供了一个框架，用于理解感觉输入如何 在背侧纹状体形成dSPN和iSPN的活动。在本提案中，我们将重点放在 背侧纹状体，称为听觉纹状体(AudStr)，接受密集的听觉输入。我们 假设听觉感觉运动学习使线索特定的集合能够形成相关的 并预测电机输出。我们预计，这些变化将主要由突触的可塑性 汇聚到SPN的输入，而不是改变其内在的兴奋性。 我们将执行两个独立的、相互关联的目标来检验这一假设。我们将训练老鼠完成一项任务 这就要求他们将“GO”提示与获得奖励的特定动作联系起来，并抑制这一点 对“不能去”的提示采取行动。在目标1中，我们将使用AudStr神经元的纵向钙成像来 描述这些神经元在学习前后对线索的输出。在目标2中，我们将探索 由于学习而导致的人群活动预期变化的细胞机制，旨在 证明突触可塑性在这一过程中的重要性。在这两个目标中，我们将使用 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，因为一个重大的突出问题 这一领域的问题是，这些细胞类型在产生适当的 运动反应。总体而言，这项工作将为理解一个新的概念模型奠定基础 感官学习如何影响纹状体活动以控制行为。

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.