Neurophysiology of DBS

项目6将重点关注DBS最基本的神经生物学效应，即如何持久，高- 皮层下白色物质的高频电刺激影响轴突、突触和神经元， 大脑皮层的前额叶区域为此，我们将使用当代体外细胞培养方法， 神经生理学，从特定的，遗传识别的皮质组进行高分辨率测量， 神经元及其突触连接。将使用几个GFP表达小鼠系。实验 将集中于DBS对传入和传出轴突传导特性的影响，并确定 兴奋性和抑制性突触连接的类型及其局部皮层回路。我们还将使用C- fos-GFP小鼠系，以询问体内高频刺激如何改变c-fos-GFP的生理特性。 表达神经元。本研究结果将有助于阐明DBS在脑内的基本作用机制 与OCD有关的结构。 相关性（见说明）： 强迫症（OCD）是一种慢性精神疾病，影响全球2-3%的人。 人口这是一种排在前十位的疾病。这项研究将检查神经 与强迫症相关的行为基础的网络和机制。这些行为不仅限于 强迫症，但与一系列的情感和成瘾性疾病。集体建议的研究 将产生新的假设，这些大脑网络中的功能障碍是如何表达的， 疾病，并提供洞察正常行为反应的机制。 项目/

Project 6 will focus on the most basic neurobiological effects of DBS, i.e. how does long-lasting, high- frequency electrical stimulation of subcortical white matter affect the axons, synapses, and neurons of prefrontal regions of neocortex? To this end, we will use contemporary methods of in vitro cellular neurophysiology to make high resolution measurements from groups of specific, genetically identified cortical neurons and their synaptic connections. Several lines of GFP-expressing mice will be used. Experiments will focus on the influence of DBS on conduction properties of afferent and efferent axons, and identified types of excitatory and inhibitory synaptic connections and their local cortical circuits. We will also use a c- fos-GFP mouse line to ask how high frequency stimulation in vivo alters the physiological properties of c-fos- expressing neurons. The results of this project should illuminate the basic mechanisms of DBS in brain structures relevant to OCD. RELEVANCE (See instmctions): Obsessive Compulsive Disorder (OCD) is a chronic psychiatric illness that affects 2-3% of the worldwide population. This is disease is in the top ten dehabilitating diseases. This study will examine the neural network and mechanisms that underiie behaviors associated with OCD. These behaviors not limited to OCD, but are associated with a range of affective and addictive disorders. The collective proposed studies will generate new hypotheses of how dysfunctions within these brain networks are expressed across diseases and provide insight into the mechanisms underlying normal behavioral responses. PROJECT/