Integration of the thalamic and cortical inputs in the auditory striatum

听觉纹状体中丘脑和皮质输入的整合

• 批准号: 10547807
• 负责人: QIAOJIE XIONG
• 金额: $ 39.88万
• 依托单位: STATE UNIVERSITY NEW YORK STONY BROOK
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-02-10 至 2025-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10547807
• 关键词: Address; Anatomy; Animals; Auditory; Auditory area; Axon; Behavior; Behavioral; Brain; Brain Diseases; Brain region; Cells; Corpus striatum structure; Decision Making; Destinations; Development; Discrimination; Dorsal; Electrophysiology (science); Frequencies; Goals; Huntington Disease; Individual; Instruction; Interneurons; Laboratories; Learning; Life; Monitor; Mus; Neurons; Parkinson Disease; Pathway interactions; Pattern; Physiological; Play; Process; Rewards; Rodent; Role; Route; Sensory; Shapes; Slice; Stimulus; Synapses; Synaptic plasticity; Testing; Thalamic structure; Work; auditory stimulus; auditory thalamus; awake; cholinergic; experimental study; flexibility; improved; in vivo; insight; nervous system disorder; optogenetics; pharmacologic; response; sound; therapy development

Animals facing a decision routinely use sensory including auditory information from the outside world to guide optimal behavior. For example, we listen for instructions from the GPS when trying to take the best route to a destination. The dorsal striatum is a critical brain region in this sensory-guided decision-making process. The long-term goal of my laboratory is to understand the circuitry and mechanisms through which the dorsal striatum transforms auditory stimuli into appropriate actions. Anatomical studies have shown that individual neurons in the dorsal striatum receive convergent inputs from both the thalamus and the cortex. Previous studies in associative striatum (rostral dorsal striatum) suggest that these two input pathways play distinct roles in behaviors. Our studies in sensory striatum (caudal dorsal striatum) indicate that projections from both the auditory thalamus and the auditory cortex are required for decision-making in rodents performing an auditory frequency-discrimination task. The primary objective of this proposal is to determine how the auditory striatum integrates these thalamic and cortical inputs, and how this integration contributes to auditory frequency-discrimination decision-making and learning. The studies proposed address the fundamental hypothesis that both thalamic and cortical inputs contribute to auditory decision- making by differentially modulating striatal sound representations, and by shaping striatal synaptic plasticity during task learning. In Aim 1, we will determine how striatal sound representation is regulated by the thalamic and cortical inputs. We will use in vivo tetrode recording on awake mice to examine the responses of striatal neurons to pure tones while thalamic or cortical inputs are selectively silenced during stimulus presentation. In Aim 2, we will examine how striatal neurons integrate the thalamic and cortical inputs using whole-cell patch recording in brain slice combined with opto-genetic and pharmacological applications. In Aim 3, we will examine the development of thalamostriatal plasticity during task learning and test how thalamic input influences the learning-induced corticostriatal plasticity, using in vivo tetrode recording on behaving mice. The proposed experiments will determine how thalamostriatal and corticostriatal pathways regulate auditory striatal activity and plasticity, the physiological mechanisms underlying their functions in auditory decision-making. We focus on the auditory striatum in this study, but the findings may be generalized to the whole sensory striatum. These results will also contribute to the understanding of brain disorders like Parkinson’s and Huntington’s disease that involve differential changes of activity and plasticity at thalamostriatal and corticostriatal synapses.

面临决定的动物通常会使用感官（包括来自外界的听觉信息）来做出决定。 指导最佳行为 例如，当我们尝试采取最佳行为时，我们会听取 GPS 的指示。 背侧纹状体是这种感官引导决策的关键大脑区域。 我实验室的长期目标是了解其电路和机制。 解剖学研究表明，背侧纹状体将听觉刺激转化为适当的动作。 背侧纹状体中的单个神经元接收来自丘脑和皮质的汇聚输入。 先前对关联纹状体（头端背侧纹状体）的研究表明，这两种输入途径发挥着作用 我们对感觉纹状体（尾背纹状体）的研究表明，预测在行为中发挥着不同的作用。 啮齿动物的决策需要来自听觉丘脑和听觉皮层的信号 该提案的主要目标是确定听觉频率辨别任务。 听觉纹状体如何整合这些丘脑和皮质输入，以及这种整合如何 有助于听觉频率辨别决策和学习。 解决丘脑和皮质输入都有助于听觉决策的基本假设 通过差异化调制纹状体声音表征和塑造纹状体突触可塑性来制作 在任务学习过程中。 在目标 1 中，我们将确定丘脑和皮质如何调节纹状体声音表征 我们将使用清醒小鼠体内四极管记录来检查纹状体神经元对输入的反应。 在目标 2 中，我们在刺激呈现期间选择性地沉默丘脑或皮质输入。 将使用全细胞贴片记录检查纹状体神经元如何整合丘脑和皮质输入 在目标 3 中，我们将研究脑切片与光遗传学和药理学应用的结合。 在任务学习过程中丘脑纹状体可塑性的发展并测试丘脑输入如何影响 学习诱导的皮质纹状体可塑性，使用行为小鼠体内四极管记录。 拟议的实验将确定丘脑纹状体和皮质纹状体通路如何调节 听觉纹状体的活动和可塑性，其听觉功能背后的生理机制 在这项研究中，我们关注的是听觉纹状体，但研究结果可以推广到听觉纹状体。 整个感觉纹状体也将有助于理解大脑疾病，例如 帕金森病和亨廷顿病涉及活动和可塑性的差异变化 丘脑纹状体和皮质纹状体突触。