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: 10093002
• 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 2024-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10093002
• 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; Genetic; Goals; Huntington Disease; Individual; Instruction; Interneurons; Laboratories; Learning; Life; Monitor; Mus; Neurons; Parkinson Disease; Pathway interactions; Pattern; Pharmacology; 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; 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.

面对决定的动物通常会使用来自外界的感官信息，包括听觉信息， 引导最佳行为。例如，当我们试图采取最佳措施时，我们会听取GPS的指示。 到达目的地的路线。背侧纹状体是这种感觉引导决策的关键大脑区域 过程我的实验室的长期目标是了解 背侧纹状体将听觉刺激转化为适当的动作。解剖学研究表明， 背侧纹状体中的单个神经元接收来自丘脑和皮层的会聚输入。 先前对联合纹状体（吻侧背侧纹状体）的研究表明，这两种输入途径发挥作用， 行为中的不同角色。我们对感觉纹状体（尾侧背侧纹状体）的研究表明， 听觉丘脑和听觉皮层的神经元是啮齿类动物做决定所必需的 执行听觉频率辨别任务。本提案的主要目的是确定 听觉纹状体如何整合这些丘脑和皮层的输入，以及这种整合是如何 有助于听觉频率辨别决策和学习。建议的研究 解决基本假设，即丘脑和皮层输入有助于听觉决策- 通过差异调节纹状体声音表征和塑造纹状体突触可塑性 在任务学习中。 在目标1中，我们将确定纹状体的声音再现是如何受到丘脑和皮层的调节的。 输入。我们将使用清醒小鼠的体内四极管记录来检查纹状体神经元对 纯音，而丘脑或皮层输入在刺激呈现期间选择性地沉默。在目标2中， 将研究纹状体神经元如何整合丘脑和皮质输入使用全细胞补丁记录 在脑切片中结合光遗传学和药理学应用。在目标3中，我们将研究 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，使用体内四极记录行为小鼠。 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，其功能的生理机制，在听觉 决策的本研究的重点是听觉纹状体，但研究结果可能会推广到 整个感觉纹状体这些结果也将有助于理解大脑疾病， 帕金森氏症和亨廷顿氏病，涉及活动和可塑性的差异性变化， 丘脑纹状体和皮质纹状体突触。