title: BK Channels Are Required for Multisensory Plasticity in the Oculomotor System.
abstract: Neural circuits are endowed with several forms of intrinsic and synaptic plasticity that could contribute to adaptive changes in behavior, but circuit complexities have hindered linking specific cellular mechanisms with their behavioral consequences. Eye movements generated by simple brainstem circuits provide a means for relating cellular plasticity to behavioral gain control. Here we show that firing rate potentiation, a form of intrinsic plasticity mediated by reductions in BK-type calcium-activated potassium currents in spontaneously firing neurons, is engaged during optokinetic reflex compensation for inner ear dysfunction. Vestibular loss triggers transient increases in postsynaptic excitability, occlusion of firing rate potentiation, and reductions in BK currents in vestibular nucleus neurons. Concurrently, adaptive increases in visually evoked eye movements rapidly restore oculomotor function in wild-type mice but are profoundly impaired in BK channel-null mice. Activity-dependent regulation of intrinsic excitability may be a general mechanism for adaptive control of behavioral output in multisensory circuits.
authors.affiliation: Neurosciences Graduate Program, University of California, San Diego, La Jolla, CA 92093, USA; Salk Institute for Biological Studies, La Jolla, CA 92037, USA; University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: alexandra.nelson@ucsf.edu.
authors.forename: Alexandra B
authors.initials: AB
authors.lastname: Nelson
authors.affiliation: Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Faulstich
authors.affiliation: Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
authors.forename: Setareh
authors.initials: S
authors.lastname: Moghadam
authors.affiliation: Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Onori
authors.affiliation: University of Maryland School of Medicine, Baltimore, MD 21201, USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Meredith
authors.affiliation: Neurosciences Graduate Program, University of California, San Diego, La Jolla, CA 92093, USA; Salk Institute for Biological Studies, La Jolla, CA 92037, USA; Johns Hopkins University, Baltimore, MD 21205, USA. Electronic address: sascha@jhmi.edu.
authors.forename: Sascha
authors.initials: S
authors.lastname: du Lac
mesh_terms: D000818:Animals; D053483:Eye Movement Measurements; D005133:Eye Movements / Q000502:physiology*; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000502:physiology*; D051379:Mice; D009473:Neuronal Plasticity / Q000502:physiology*; D012027:Reflex, Vestibulo-Ocular / Q000502:physiology*; D011984:Sensory Receptor Cells / Q000502:physiology*; D014726:Vestibular Nuclei / Q000166:cytology / Q000502:physiology*; D014722:Vestibule, Labyrinth / Q000293:injuries
chemical_list: D051036:Large-Conductance Calcium-Activated Potassium Channels
keywords: calcium-activated; calcium-dependent potassium; firing rate potentiation; intrinsic plasticity; optokinetic; vestibular; vestibulo-ocular reflex