Modulation of Neocortical Interneuronal Function

描述（由申请人提供）：抑制性中间神经元在正常的新皮层功能中起着许多关键作用。例如，它们塑造感觉感受野并驱动高频伽马振荡。另一方面，其功能的缺陷可能导致癫痫发作。我们已经研究了两个主要的功能interneuronal亚类的属性：快速尖峰（FS）和低阈值尖峰放电（ITS）神经元的大鼠新皮层第五层的数据表明，每组表达一种新的形式的自我抑制，即autaptic抑制反应FS细胞和内源性大麻素介导的缓慢自我抑制ITS interneurons。我们将解决两个主要问题相关的自我抑制的新皮层中间神经元：1）FS细胞autapses在调节精度的尖峰时间和协调快速网络同步的作用是什么？2)导致ITS神经元中持久抑制的机制是什么？其诱导所需的生理条件是什么？总的来说，这两个实验目标将解决这个补助金的中心主题，调节和控制新皮层神经元间活动的机制，以及这种调节对新皮层电路功能的功能后果。实验方法将包括：单个和成对的全细胞电压和电流钳记录和穿孔的补丁记录可视化interneurons在大鼠新皮层切片;细胞内标记与biocytin;细胞内和细胞外应用的离子和药物制剂，以影响发射器的释放和受体功能;和使用动态钳。结果将导致更好地了解突触调制的两个主要亚类的新皮层中间神经元和GABA能调节相关的正常和病理生理皮层功能的新皮层兴奋性提供信息。

DESCRIPTION (provided by applicant): Inhibitory interneurons play a number of key roles in normal neocortical function. For example, they shape sensory receptive fields and drive high frequency gamma oscillations. On the other hand, defects in their function can lead to seizures. We have examined the properties of two major functional interneuronal subclasses: fast spiking (FS) and low-threshold spike firing (ITS) neurons of rat neocortical layer V. Data indicate that each group expresses a novel form of self inhibition, namely autaptic inhibitory responses in FS cells and an endocannabinoid-mediated slow self-inhibition in ITS interneurons. We will address two major questions relevant to self-inhibition of neocortical interneurons: 1) What are the roles of FS cell autapses in regulating precision of spike timing and in coordinating fast network synchrony? 2) What are the mechanisms leading to long-lasting inhibition in ITS neurons, and the physiological conditions necessary for its induction? Overall these two experimental aims will address the central themes of this grant, the mechanisms that modulate and control neocortical interneuronal activities and the functional consequences of such modulation on neocortical circuit function. Experimental approaches will include: single and paired whole cell voltage- and current-clamp recordings and perforated-patch recordings from visualized interneurons in rat neocortical slices; intracellular labeling with biocytin; intracellular and extracellular application of ions and pharmaceutical agents to affect transmitter release and receptor function; and use of dynamic clamp. Results will lead to a better understanding of synaptic modulation of two major subclasses of neocortical interneurons and provide information regarding GABAergic regulation of neocortical excitability relevant to both normal and pathophysiological cortical function.