title: The BK-mediated fAHP is modulated by learning a hippocampus-dependent task.
abstract: Intrinsic excitability is a plastic property of cells that, along with synaptic changes, can be modulated by learning. Action potential (AP) height, width, and frequency are intrinsically controlled properties which rely on the activation of Na(+), Ca(2+), and K(+) channels in the dendritic, somatic, and axonal membranes. The fast after-hyperpolarization (fAHP) after an AP is partially responsible for determining the half-width and duration of the AP and thus Ca(2+) influx during the depolarization. In CA1 hippocampal pyramidal cells, the fAHP is carried by the voltage- and Ca(2+)-dependent BK channel. In addition to modulating the duration of the AP, the BK-mediated potassium current exerts control over the frequency of AP generation in response to a depolarizing input. These facts position BK-mediated effects to not only modulate immediate intraneuronal communication, but also to control longer-term Ca(2+)-dependent changes in the neuron, such as kinase activation, gene transcription, and synaptic plasticity. We examined how the BK-mediated fAHP was altered in hippocampal neurons after learning trace eyeblink conditioning. By using current clamp methods, it was found that the fAHP is reduced and the AP duration is increased in cells from conditioned animals. Additionally, in vitro and in vivo measures of firing frequency show that BK-channel blockade increases both evoked (in vitro) and spontaneous (in vivo) firing frequency of CA1 neurons, implicating the BK channel in the control of intrinsic excitability. These data indicate that the reduction of the BK-mediated fAHP is an essential part of the total increase of neuronal excitability known to accompany hippocampus-dependent learning.
authors.affiliation: Department of Physiology, Northwestern University, Chicago, IL 60611, USA. e-matthews@md.northwestern.edu
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Matthews
authors.forename: Aldis P
authors.initials: AP
authors.lastname: Weible
authors.forename: Samit
authors.initials: S
authors.lastname: Shah
authors.forename: John F
authors.initials: JF
authors.lastname: Disterhoft
mesh_terms: D000200:Action Potentials; D000818:Animals; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000378:metabolism*; D007858:Learning; D008297:Male; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000378:metabolism / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D051036:Large-Conductance Calcium-Activated Potassium Channels
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