BK Channels Mediate Synaptic Plasticity Underlying Habituation in Rats
Autor: | Chakravarthi Narla, Cleusa V.R. de Oliveira, Michael O. Poulter, Mahabba Smoka, Susanne Schmid, Tariq Zaman |
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Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Male BK channel Reflex Startle Patch-Clamp Techniques synaptic depression Sensory system Neuroimaging In Vitro Techniques 03 medical and health sciences Cell and Developmental Biology 0302 clinical medicine Pons Neuroplasticity Reflex medicine Animals Psychology rat Large-Conductance Calcium-Activated Potassium Channels Habituation Phosphorylation Habituation Psychophysiologic Research Articles Psychophysiologic Neuronal Plasticity biology Mechanism (biology) General Neuroscience Startle Neurosciences medicine.disease Voltage-Sensitive Dye Imaging Rats 030104 developmental biology Acoustic Stimulation Schizophrenia Synaptic plasticity Synapses biology.protein Autism learning and memory Anatomy Neuroscience sensory filtering 030217 neurology & neurosurgery |
Zdroj: | Brain and Mind Institute Researchers' Publications Anatomy and Cell Biology Publications |
Popis: | 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. |
Databáze: | OpenAIRE |
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