Synchronized network activity in developing rat hippocampus involves regional hyperpolarization-activated cyclic nucleotide-gated (HCN) channel function

The principal form of synchronized network activity in neonatal hippocampus consists of low frequency 'giant depolarizing potentials' (GDPs). Whereas contribution of both GABA and glutamate to their generation has been demonstrated, full understanding of the mechanisms underlying these synchronized activity bursts remains incomplete. A contribution of the h-current, conducted by HCN channels, to GDPs has been a topic of substantial interest. Here we focus on HCN1, the prevalent HCN channel isoform in neonatal hippocampus, and demonstrate an HCN1 spatiotemporal expression pattern in both CA3 principal cells and interneurons that correlates with the developmental profile of GDPs. Abrogation of HCN physiological function in CA3, via the selective I-h-blocker ZD7288, disrupts GDP generation. Furthermore, ZD7288 specifically abolishes spontaneous bursting of the CA3 pyramidal cells at frequencies typical of GDPs without major influence on interneuronal firing. These findings support a pivotal role for HCN channels expressed by CA3 neurons, and particularly CA3 pyramidal cells, in GDP-related network synchronization.