title: Distinct roles for I(T) and I(H) in controlling the frequency and timing of rebound spike responses.
abstract: The ability for neurons to generate rebound bursts following inhibitory synaptic input relies on ion channels that respond in a unique fashion to hyperpolarization. Inward currents provided by T-type calcium channels (I(T)) and hyperpolarization-activated HCN channels (I(H)) increase in availability upon hyperpolarization, allowing for a rebound depolarization after a period of inhibition. Although rebound responses have long been recognized in deep cerebellar nuclear (DCN) neurons, the actual extent to which I(T) and I(H) contribute to rebound spike output following physiological levels of membrane hyperpolarization has not been clearly established. The current study used recordings and simulations of large diameter cells of the in vitro rat DCN slice preparation to define the roles for I(T) and I(H) in a rebound response. We find that physiological levels of hyperpolarization make only small proportions of the total I(T) and I(H) available, but that these are sufficient to make substantial contributions to a rebound response. At least 50% of the early phase of the rebound spike frequency increase is generated by an I(T)-mediated depolarization. An additional frequency increase is provided by I(H) in reducing the time constant and thus the extent of I(T) inactivation as the membrane returns from a hyperpolarized state to the resting level. An I(H)-mediated depolarization creates an inverse voltage-first spike latency relationship and produces a 35% increase in the precision of the first spike latency of a rebound. I(T) and I(H) can thus be activated by physiologically relevant stimuli and have distinct roles in the frequency, timing and precision of rebound responses.
authors.affiliation: Hotchkiss Brain Institute, University of Calgary, 3330 Hospital Drive N.W., Calgary, AB, Canada T2N 4N1. rwturner@ucalgary.ca
authors.forename: Jordan D T
authors.initials: JD
authors.lastname: Engbers
authors.forename: Dustin
authors.initials: D
authors.lastname: Anderson
authors.forename: Reza
authors.initials: R
authors.lastname: Tadayonnejad
authors.forename: W Hamish
authors.initials: WH
authors.lastname: Mehaffey
authors.forename: Michael L
authors.initials: ML
authors.lastname: Molineux
authors.forename: Ray W
authors.initials: RW
authors.lastname: Turner
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D020747:Calcium Channels, T-Type / Q000502:physiology*; D002529:Cerebellar Nuclei / Q000166:cytology / Q000502:physiology*; D003198:Computer Simulation; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000502:physiology*; D005260:Female; D008297:Male; D008564:Membrane Potentials / Q000502:physiology*; D008959:Models, Neurological; D009474:Neurons / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D020747:Calcium Channels, T-Type; D054815:Cyclic Nucleotide-Gated Cation Channels