Circuit plasticity underlying acquisition of sensory decision task

项目概要/摘要 这些研究的长期目标是了解潜在的电路可塑性， 任意感觉刺激与任意动作的关联。了解这种电路 可能会对临床重要中枢神经系统疾病的诊断和治疗产生影响 神经病理学，包括亨廷顿病，帕金森病，成瘾， 精神分裂症和强迫症 这项提议的中心目标是检验皮质的差异可塑性 投射到纹状体中两个不同的神经元亚群是获得一个 感觉运动辨别行为我们用老鼠作为模型系统， 对遗传上确定的神经元亚群的复杂询问。在目标1中，我们使用 体外电生理方法在急性脑片中研究皮质纹状体的强度 动物接受简单任务训练后，将声音与左或右的选择联系起来。在 目标2我们将使用相同的方法来研究动物训练的任务需要更大的 行为灵活性最后，在目标3中，我们测试声音和动作的关联是否会导致 纹状体神经元的两个亚群的差异变化。 这些研究将提供深入了解动物如何获得任意协会，并提供一个 为进一步研究这些神经元在正常功能和疾病中的作用奠定了基础， 精神和神经疾病治疗方法的发展。

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.