Functional roles and regulation of HCN channels iin neuronal circuits

超极化激活的环核苷酸门控（HCN）通道在CNS中广泛表达。虽然这些通道的电生理特性已经在异源表达系统中进行了相当详细的研究，但到目前为止，在神经元回路的背景下，通道的功能作用和调节仅被很好地定义。因此，本提案的第一个目的是鉴定和表征不同脑区域中HCN通道的调节蛋白。其次，将生成并分析两种遗传小鼠模型（HCN 2/4cad）以确定体内HCN通道的cAMP依赖性调节的相关性。最后，我们将产生两个小鼠系（HCN 2 -1/4开关小鼠），以研究HCN通道的不同生物物理特性与其在神经元网络中的功能角色之间的相关性。

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.