title: BK Channels Mediate Synaptic Plasticity Underlying Habituation in Rats.
abstract: Habituation is a basic form of implicit learning and represents a sensory filter that is disrupted in autism, schizophrenia, and several other mental disorders. Despite extensive research in the past decades on habituation of startle and other escape responses, the underlying neural mechanisms are still not fully understood. There is evidence from previous studies indicating that BK channels might play a critical role in habituation. We here used a wide array of approaches to test this hypothesis. We show that BK channel activation and subsequent phosphorylation of these channels are essential for synaptic depression presumably underlying startle habituation in rats, using patch-clamp recordings and voltage-sensitive dye imaging in slices. Furthermore, positive modulation of BK channelsin vivocan enhance short-term habituation. Although results using different approaches do not always perfectly align, together they provide convincing evidence for a crucial role of BK channel phosphorylation in synaptic depression underlying short-term habituation of startle. We also show that this mechanism can be targeted to enhance short-term habituation and therefore to potentially ameliorate sensory filtering deficits associated with psychiatric disorders.SIGNIFICANCE STATEMENTShort-term habituation is the most fundamental form of implicit learning. Habituation also represents a filter for inundating sensory information, which is disrupted in autism, schizophrenia, and other psychiatric disorders. Habituation has been studied in different organisms and behavioral models and is thought to be caused by synaptic depression in respective pathways. The underlying molecular mechanisms, however, are poorly understood. We here identify, for the first time, a BK channel-dependent molecular synaptic mechanism leading to synaptic depression that is crucial for habituation, and we discuss the significance of our findings for potential treatments enhancing habituation.
authors.affiliation: Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario N6A 5C1, Canada, and.
authors.forename: Tariq
authors.identifier: 0000-0003-1025-8542
authors.initials: T
authors.lastname: Zaman
authors.affiliation: Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario N6A 5C1, Canada, and.
authors.forename: Cleusa
authors.identifier: 0000-0001-5962-7754
authors.initials: C
authors.lastname: De Oliveira
authors.affiliation: Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario N6A 5C1, Canada, and.
authors.forename: Mahabba
authors.identifier: 0000-0001-8943-3635
authors.initials: M
authors.lastname: Smoka
authors.affiliation: Physiology and Pharmacology, and Molecular Medicine Research Group, Robarts Research Institute, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario N6A 5C1, Canada.
authors.forename: Chakravarthi
authors.initials: C
authors.lastname: Narla
authors.affiliation: Physiology and Pharmacology, and Molecular Medicine Research Group, Robarts Research Institute, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario N6A 5C1, Canada.
authors.forename: Michael O
authors.identifier: 0000-0001-7469-8462
authors.initials: MO
authors.lastname: Poulter
authors.affiliation: Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario N6A 5C1, Canada, and Susanne.Schmid@schulich.uwo.ca.
authors.forename: Susanne
authors.identifier: 0000-0001-5366-8061
authors.initials: S
authors.lastname: Schmid
mesh_terms: D000161:Acoustic Stimulation; D000818:Animals; D006185:Habituation, Psychophysiologic / Q000502:physiology*; D066298:In Vitro Techniques; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000378:metabolism*; D008297:Male; D059906:Neuroimaging; D009473:Neuronal Plasticity / Q000502:physiology*; D018408:Patch-Clamp Techniques; D010766:Phosphorylation; D011149:Pons / Q000502:physiology; D051381:Rats; D013216:Reflex, Startle / Q000502:physiology; D013569:Synapses / Q000502:physiology*; D056969:Voltage-Sensitive Dye Imaging
chemical_list: D051036:Large-Conductance Calcium-Activated Potassium Channels
keywords: habituation; learning and memory; rat; sensory filtering; startle; synaptic depression