Journal
EUROPEAN JOURNAL OF NEUROSCIENCE
Volume 22, Issue 10, Pages 2669-2674Publisher
WILEY
DOI: 10.1111/j.1460-9568.2005.04407.x
Keywords
CA3; development; giant depolarizing potentials; interneuron; synchronization
Categories
Funding
- NIAAA NIH HHS [AA015614, R01 AA015614, R37 AA015614] Funding Source: Medline
- NINDS NIH HHS [R37 NS035439, NS35439, R01 NS035439, R01 NS035439-06, R01 NS035439-07] Funding Source: Medline
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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.
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