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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

基本信息

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
项目类别：
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

项目摘要

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使用包括来自外部世界的听觉信息在内的感觉信息来引导最优行为。例如，当我们试图获取最好的信息时，我们会听从GPS的指示到达目的地的路线。在这种感觉引导的决策中，背侧纹状体是一个关键的大脑区域。进程。我的实验室的长期目标是了解通过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受来自丘脑和皮质的汇聚输入。先前对联合纹状体(嘴背侧纹状体)的研究表明，这两条输入通路起作用。在行为中扮演不同的角色。我们对感觉纹状体(尾侧背侧纹状体)的研究表明，投射在啮齿动物的决策过程中，听觉丘脑和听觉皮质都是必需的。执行听觉频率辨别任务。这项提案的主要目标是确定听觉纹状体如何整合这些丘脑和皮质的输入，以及这种整合如何有助于听觉频率辨别决策和学习。这项研究建议解决丘脑和大脑皮层输入都有助于听觉决策的基本假设- 通过差异调制纹状体声音表征和塑造纹状体突触可塑性在任务学习过程中。在目标1中，我们将确定丘脑和大脑皮层如何调节纹状体声音的表达。投入。我们将使用清醒小鼠的活体四极管记录来检测纹状体神经元对纯音，而丘脑或大脑皮层的输入在刺激呈现时被选择性地静音。在目标2中，我们将使用全细胞贴片记录研究纹状体神经元如何整合丘脑和皮质的输入在脑片上结合光遗传学和药理学的应用。在目标3中，我们将研究任务学习中丘脑纹状体可塑性的发展以及丘脑输入如何影响任务学习学习诱导的皮质纹状体可塑性，使用行为小鼠的活体四极管记录。拟议中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活动和可塑性及其在听觉功能中的生理机制决策。在这项研究中，我们将重点放在听觉纹状体上，但这些发现可能被推广到整个感觉纹状体。这些结果也将有助于理解大脑紊乱，如帕金森氏病和亨廷顿氏病，涉及活动和可塑性的不同变化丘脑纹状体和皮质纹状体突触。