HCN1 channels constrain synaptically evoked Ca2+ spikes in distal dendrites of CA1 pyramidal neurons.
HCN1 hyperpolarization-activated cation channels act as an inhibitory constraint of both spatial learning and synaptic integration and long-term plasticity in the distal dendrites of hippocampal CA1 pyramidal neurons. However, as HCN1 channels provide an excitatory current, the mechanism of their inhibitory action remains unclear. Here we report that HCN1 channels also constrain CA1 distal dendritic Ca2+ spikes, which have been implicated in the induction of LTP at distal excitatory synapses. Our experimental and computational results indicate that HCN1 channels provide both an active shunt conductance that decreases the temporal integration of distal EPSPs and a tonic depolarizing current that increases resting inactivation of T-type and N-type voltage-gated Ca2+ channels, which contribute to the Ca2+ spikes. This dual mechanism may provide a general means by which HCN channels regulate dendritic excitability.
Tsay
David
D
Department of Neuroscience, Columbia University, 1051 Riverside Drive, New York, NY 10032, USA.
Dudman
Joshua T
JT
Siegelbaum
Steven A
SA
D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D003198:Computer Simulation; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000172:deficiency / Q000502:physiology*; D003712:Dendrites / Q000502:physiology*; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation / Q000379:methods; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D006624:Hippocampus / Q000166:cytology*; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D066298:In Vitro Techniques; D051379:Mice; D018345:Mice, Knockout; D018408:Patch-Clamp Techniques / Q000379:methods; D015221:Potassium Channels / Q000172:deficiency / Q000502:physiology*; D017966:Pyramidal Cells / Q000166:cytology*; D011743:Pyrimidines / Q000494:pharmacology; D011930:Reaction Time / Q000187:drug effects; D013569:Synapses / Q000187:drug effects / Q000235:genetics / Q000502:physiology*
D002121:Calcium Channel Blockers; D054815:Cyclic Nucleotide-Gated Cation Channels; D018691:Excitatory Amino Acid Antagonists; C578666:Hcn1 protein, mouse; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D015221:Potassium Channels; D011743:Pyrimidines; C082246:ICI D2788; D002118:Calcium