Circuit plasticity underlying acquisition of sensory decision task

感知决策任务获取的电路可塑性

基本信息

批准号：
9065689
负责人：
ANTHONY M ZADOR
金额：
$ 42万
依托单位：
COLD SPRING HARBOR LABORATORY
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-07-01 至 2019-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9065689
关键词：
Acoustics Acute Animals Area Association Learning Auditory Auditory area Behavior Behavioral Behavioral Paradigm Biological Models Brain Calcium Chronic Complex Corpus striatum structure Data Decision Making Diagnosis Discrimination Disease Dopamine Receptor Electrophysiology (science)Equilibrium Etiology Foundations Frequencies Fruit Goals Huntington Disease Image In Vitro Individual Investigation Label Laboratories Lead Learning Left Link Mental disorders Methods Modeling Molecular Monitor Movement Mus Neurons Obsessive-Compulsive Disorder Output Parkinson Disease Pathway interactions Pattern Physiological Play Publishing Recording of previous events Rewards Rodent Role Schizophrenia Sensory Sensory Process Site Slice Stream Structure Synapses System Testing Training Transgenic Mice abstracting addiction flexibility improved in vivo insight nervous system disorder neuromechanism neuropathology optogenetics postsynaptic sensory input sensory stimulus sound sound frequency therapy development tool

项目摘要

Project Summary/Abstract The long-term goal of these investigations is to understand the circuit plasticity underlying the association of an arbitrary sensory stimulus with an arbitrary action. Understanding this circuitry is likely to have an impact on the diagnosis and treatment of clinically important central neuropathologies, including Huntington's disease, Parkinson's disease, addiction, schizophrenia, and obsessive compulsive disorder. The central goal of this proposal is to test the hypothesis that differential plasticity at the cortical projection to two different neuronal subpopulations in the striatum underlie the acquisition of a sensorimotor discrimination behavior. We use mice as a model system because they allow sophisticated interrogation of genetically defined subpopulations of neurons. In Aim 1 we use in vitro electrophysiological methods in acute brain slices to study the strength of corticostriatal synapses in animals trained on a simple task associating sounds with a left or right choice. In Aim 2 we will use the same methods to study animals trained on a task requiring greater behavioral flexibility. Finally in Aim 3, we test whether association of the sound and action leads to differential changes at the two subpopulations of striatal neurons. These studies will provide insight into how animals acquire arbitrary associations, and provide a foundation for further study of role of these neurons in normal function and disease, facilitating the development of treatments for psychiatric and neurological diseases.

项目摘要/摘要这些调查的长期目标是了解电路可塑性任意感觉刺激与任意作用的关联。了解此电路可能会影响临床上重要的中心的诊断和治疗神经病理学，包括亨廷顿氏病，帕金森氏病，成瘾，精神分裂症和强迫症。该提议的核心目的是检验以下假设：皮质的差异可塑性纹状体中对两个不同神经元亚群的投影是获得感觉运动歧视行为。我们使用小鼠作为模型系统，因为它们允许对神经元基因定义的亚群的复杂询问。在AIM 1中我们使用急性脑切片中的体外电生理方法研究皮质纹状体的强度在接受左右选择的简单任务中训练的动物突触。在目的2我们将使用相同的方法研究接受培训的动物，需要更大行为灵活性。最终在AIM 3中，我们测试声音和动作的关联是否引导在纹状体神经元的两个亚群中的差异变化。这些研究将提供有关动物如何获得任意关联的洞察力，并提供进一步研究这些神经元在正常功能和疾病中的作用的基础，促进精神病和神经系统疾病治疗的发展。