Function of lateral Inhibition in layer 2/3 of adult mouse barrel cortex

新皮质层2/3代表躯体感觉系统中的第一个神经元站，其以整合的方式处理传入的感觉信息。在桶状皮层中，这些层代表了整合来自邻近胡须的触觉信息的第一站。因此，第2/3层在感觉刺激的辨别中发挥重要作用。这种区分的时空精度主要由板内侧抑制介导，其中具有快速尖峰（FS）放电模式的小白蛋白免疫反应（PV+）GABA能中间神经元起核心作用。本研究将采用电生理学、行为学和光遗传学方法研究成年小鼠的触须系统，以阐明第2/3层的侧抑制功能。两个新的行为测试将允许的空间和时空之间的歧视能力的实验分析机械刺激传递到两个相邻的触须在头部固定，operantly条件反射的动物。与该辨别任务相关的神经元活动将用80通道多电极阵列记录在相应的皮层列中。在B6. Cg-Pvalbtm 1.1（cre）Aibs/J系转基因小鼠中通过病毒转染（rAAV 2/Flex-Arch-GFP）在FS-PV+中间神经元中选择性表达氯泵古视紫红质-3（Arch）将允许对层2/3中的侧向抑制进行特异性和局部光遗传学操纵，并分析所得的行为和电生理学修饰。在细胞和局部网络水平上FS-PV+中间神经元的光遗传学抑制的结果将在桶状皮质的体外丘脑皮质切片制备物中研究。这些在体内和体外实验将产生新的见解的时空特性的生理相关的任务中的侧抑制。

Neocortical layer 2/3 represents the first neuronal station in the somatosensory system which processes incoming sensory information in an integrative manner. In the barrel cortex, these layers represent the first station integrating tactile information from neighbouring whiskers. Therefore, layer 2/3 fulfils an important role in the discrimination of sensory stimuli. The spatio-temporal precision of this discrimination is mostly mediated by intralaminar lateral inhibition, in which parvalbumin-immunoreactive (PV+) GABAergic interneurons with fast spiking (FS) discharge patterns play a central role. Electrophysiological, behavioural and optogenetic methods will be used in the vibrissal system of adult mice to elucidate the function of lateral inhibition in layer 2/3. Two novel behavioural tests will allow the experimental analysis of the spatial and spatio-temporal discrimination capability between mechanical stimuli delivered to two neighbouring vibrissae in head-fixed, operantly conditioned animals. The neuronal activity associated with this discrimination task will be recorded in the corresponding cortical columns with an 80-channel multi-electrode-array. The selective expression of the chloride pump Archaerhodopsin-3 (Arch) in FS-PV+ interneurons via viral transfection (rAAV2/Flex-Arch-GFP) in transgenic mice of the line B6.Cg-Pvalbtm1.1(cre)Aibs/J will allow a specific and local optogenetic manipulation of lateral inhibition in layer 2/3 and the analysis of the resulting behavioural and electrophysiological modifications. The consequence of optogenetic inhibition of FS-PV+ interneurons at the cellular and local network level will be studied in in vitro thalamocortical slice preparations of the barrel cortex. These in vivo and in vitro experiments will yield novel insights to the spatio-temporal properties of lateral inhibition in physiologically relevant tasks.