title: I(h)-mediated depolarization enhances the temporal precision of neuronal integration.
abstract: Feed-forward inhibition mediated by ionotropic GABA(A) receptors contributes to the temporal precision of neuronal signal integration. These receptors exert their inhibitory effect by shunting excitatory currents and by hyperpolarizing neurons. The relative roles of these mechanisms in neuronal computations are, however, incompletely understood. In this study, we show that by depolarizing the resting membrane potential relative to the reversal potential for GABA(A) receptors, the hyperpolarization-activated mixed cation current (I(h)) maintains a voltage gradient for fast synaptic inhibition in hippocampal pyramidal cells. Pharmacological or genetic ablation of I(h) broadens the depolarizing phase of afferent synaptic waveforms by hyperpolarizing the resting membrane potential. This increases the integration time window for action potential generation. These results indicate that the hyperpolarizing component of GABA(A) receptor-mediated inhibition has an important role in maintaining the temporal fidelity of coincidence detection and suggest a previously unrecognized mechanism by which I(h) modulates information processing in the hippocampus.
authors.affiliation: Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, London WC1N 3GB, UK.
authors.forename: Ivan
authors.initials: I
authors.lastname: Pavlov
authors.forename: Annalisa
authors.initials: A
authors.lastname: Scimemi
authors.forename: Leonid
authors.initials: L
authors.lastname: Savtchenko
authors.forename: Dimitri M
authors.initials: DM
authors.lastname: Kullmann
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Walker
mesh_terms: D000818:Animals; D002412:Cations / Q000378:metabolism*; D003198:Computer Simulation; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000378:metabolism*; D004594:Electrophysiology; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D008297:Male; D008564:Membrane Potentials / Q000502:physiology*; D008954:Models, Biological; D015221:Potassium Channels / Q000378:metabolism*; D017966:Pyramidal Cells / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology*
chemical_list: D002412:Cations; D054815:Cyclic Nucleotide-Gated Cation Channels; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D015221:Potassium Channels; D011963:Receptors, GABA-A