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。尽管它的重要性， 健康和疾病，我们对我们如何分配意义和使用感官刺激知之甚少， 引导行为。背侧纹状体被认为对感觉运动的形成特别重要 在强化学习过程中，由于它接收的多巴胺能输入，以及不同的 皮层和皮层下输入的阵列。有两种类型的细胞构成了两个输出途径， 背侧纹状体、直接通路纹状体投射神经元（dSPNs）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，启动运动，很少 我们知道感觉学习如何影响这些神经元的神经元活动， 关于行为。 构成这一提议的实验为理解感觉输入如何 形成背侧纹状体中dSPN和iSPN的活性。在本提案中，我们侧重于以下方面的一个具体部分： 背侧纹状体被称为听觉纹状体（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特定线索的集合， 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，而不是改变其内在的兴奋性。 我们将执行两个独立的，相互关联的目标来测试这个假设。我们将训练老鼠完成一项任务 这就要求他们将一个“开始”的提示与一个特定的动作联系起来，以获得奖励，并抑制这种行为。 对"禁止进入"提示的反应。在目标1中，我们将采用AudStr神经元的纵向钙成像， 描述这些神经元在学习之前和之后的输出。在目标2中，我们将探讨 细胞机制潜在的预期变化的人口活动的结果，从学习，并旨在 证明了AudStr中突触可塑性对这一过程的重要性。在这两个目标中，我们将使用 这些方法使我们能够将神经元识别为dSPN和iSPN。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 运动反应总的来说，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。

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.