Circuit plasticity underlying acquisition of sensory decision task

项目摘要/摘要 这些研究的长期目标是了解 将任意的感官刺激与任意的行为联系起来。了解此电路 可能会对临床上重要的中枢神经系统疾病的诊断和治疗产生影响 神经病理学，包括亨廷顿氏症，帕金森氏症，成瘾， 精神分裂症和强迫症。 这一提议的中心目标是检验这样一种假设，即大脑皮质的差异可塑性 向纹状体中两个不同神经元亚群的投射是获得 感觉运动辨别行为。我们使用老鼠作为模型系统，因为它们允许 对遗传定义的神经元亚群进行复杂的讯问。在目标1中，我们在 急性脑片体外电生理方法研究皮质纹状体的强度 在一项简单的任务中训练动物的突触，将声音与左或右选择联系起来。在……里面 目标2我们将使用相同的方法来研究在一项要求更高的任务中训练的动物 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不同变化。 这些研究将提供对动物如何获得任意联系的洞察，并提供 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基础，促进 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.