title: Fast rhythmic bursting can be induced in layer 2/3 cortical neurons by enhancing persistent Na+ conductance or by blocking BK channels.
abstract: Fast rhythmic bursting (or "chattering") is a firing pattern exhibited by selected neocortical neurons in cats in vivo and in slices of adult ferret and cat brain. Fast rhythmic bursting (FRB) has been recorded in certain superficial and deep principal neurons and in aspiny presumed local circuit neurons; it can be evoked by depolarizing currents or by sensory stimulation and has been proposed to depend on a persistent g(Na) that causes spike depolarizing afterpotentials. We constructed a multicompartment 11-conductance model of a layer 2/3 pyramidal neuron, containing apical dendritic calcium-mediated electrogenesis; the model can switch between rhythmic spiking (RS) and FRB modes of firing, with various parameter changes. FRB in this model is favored by enhancing persistent g(Na) and also by measures that reduce [Ca(2+)](i) or that reduce the conductance of g(K(C)) (a fast voltage- and Ca(2+)-dependent conductance). Axonal excitability plays a critical role in generating fast bursts in the model. In vitro experiments in rat layer 2/3 neurons confirmed (as shown previously by others) that RS firing could be switched to fast rhythmic bursting, either by buffering [Ca(2+)](i) or by enhancing persistent g(Na). In addition, our experiments confirmed the model prediction that reducing g(KC) (with iberiotoxin) would favor FRB. During the bursts, fast prepotentials (spikelets) could occur that did not originate in apical dendrites and that appear to derive from the axon. We suggest that modulator-induced regulation of [Ca(2+)] dynamics or of BK channel conductance, for example via protein kinase A, could play a role in determining the firing pattern of neocortical neurons; specifically, such modulation could play a role in regulating whether neurons respond to strong stimulation with fast rhythmic bursts.
authors.affiliation: Department of Physiology and Pharmacology, State University of New York Health Science Center, Brooklyn, New York 11203, USA. roger.traub@downstate.edu
authors.forename: Roger D
authors.initials: RD
authors.lastname: Traub
authors.forename: Eberhard H
authors.initials: EH
authors.lastname: Buhl
authors.forename: Tengis
authors.initials: T
authors.lastname: Gloveli
authors.forename: Miles A
authors.initials: MA
authors.lastname: Whittington
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D001369:Axons / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D002540:Cerebral Cortex / Q000166:cytology / Q000502:physiology*; D051036:Large-Conductance Calcium-Activated Potassium Channels; D008297:Male; D008959:Models, Neurological; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009924:Organ Culture Techniques; D010396:Penicillamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D010507:Periodicity; D024681:Potassium Channels, Calcium-Activated / Q000037:antagonists & inhibitors*; D017966:Pyramidal Cells / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000378:metabolism*; D015222:Sodium Channels / Q000502:physiology
chemical_list: D051036:Large-Conductance Calcium-Activated Potassium Channels; D020030:Nitric Oxide Donors; D024681:Potassium Channels, Calcium-Activated; C110881:S-nitro-N-acetylpenicillamine; D015222:Sodium Channels; D012964:Sodium; D010396:Penicillamine; D002118:Calcium