Functional roles and regulation of HCN channels iin neuronal circuits

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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.