Functional roles and regulation of HCN channels iin neuronal circuits

超极化激活的环核苷酸门控(HCN)通道广泛表达于中枢神经系统。虽然在异源表达系统中对这些通道的电生理特性进行了相当详细的研究，但到目前为止，这些通道在神经元回路中的功能作用和调制还没有明确的定义。因此，这项建议的第一个目标是识别和表征不同脑区的HCN通道调节蛋白。其次，将建立两种遗传性小鼠模型(HCN2/4cad)，并对其进行分析，以确定体内cAMP依赖的HCN通道调控的相关性。最后，我们将建立两个小鼠系(HCN2-1/4开关小鼠)来研究HCN通道的不同生物物理性质与它们在神经网络中的功能作用之间的相关性。

Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are widely expressed in the CNS. While the electrophysiological properties of these channels have been investigated in quite detail in heterologous expression systems, the functional roles and the modulation of the channels in the context of neuronal circuits have been only poorly defined so far. Therefore, the first aim of this proposal is to identify and characterize regulatory proteins of HCN channels in different brain regions. Secondly, two genetic mouse models (HCN2/4cad) will be generated and analyzed to define the relevance of cAMP-dependent regulation of HCN channels in vivo. Finally, we will generate two mouse lines (HCN2-1/4 Switch mice) to study the correlation between the distinct biophysical properties of HCN channels and their functional roles in neuronal networks.