NF186 in GABAergic domain specific synaptic targeting

GABA能抑制在神经网络特性的许多方面起着重要作用， 神经元的兴奋性同步。不同类别的GABA能突触被分离成亚细胞突触， 结构域（即树突、索马、轴突起始段-AIS），从而差异地调节输入， 主要神经元的整合和输出。的亚细胞靶向的机制， γ-氨基丁酸能突触仍然在很大程度上未知。我们实验室最近的工作表明， L1家族免疫球蛋白细胞粘附分子（IgCAM）神经纤维素186（NF 186）的重要作用 和其基础的基于抗坏血酸G的膜骨架在将GABA能突触靶向AIS中的作用。 小脑浦肯野神经元。在这里，我们假设，亚细胞定位和信号转导的 NF 186是一种将GABA能神经支配定向到主要神经元的索马/AIS的一般机制， 就像新皮层的锥体神经元一样。我们将通过检查空间和时间来验证这一假设。 在GABA能突触靶向过程中NF 186的表达，并通过操纵分布和功能 通过遗传、生物化学和成像方法的组合来检测NF 186的水平。

GABAergic inhibition plays important roles in many aspects of neural network properties ranging from neuronal excitability to synchrony. Distinct classes of GABAergic synapses are segregated into subcellular domains (i.e. dendrite, soma, axon initial segment-AIS), thereby differentially regulating the input, integration and output of principal neurons. The mechanisms underlying the subcellular targeting of GABAergic synapses remain largely unknown. Recent work in our laboratory has demonstrated an essential role for an L1 family immunoglobulin cell adhesion molecule (IgCAM), neurofascin186 (NF186) and its underlying ankyrinG-based membrane skeleton in the targeting of GABAergic synapses to AIS of Purkinje neurons in cerebellum. Here we hypothesize that the subcellular localization and signaling of NF186 is a general mechanism which directs GABAergic innervation to soma/AIS of principal neurons, such as pyramidal neurons in neocortex. We will test this hypothesis by examining the spatial and temporal expression of NF186 during GABAergic synapse targeting, and by manipulating the distribution and function of NF186 through a combination of genetic, biochemical and imaging approaches.