期刊
JOURNAL OF NEUROSCIENCE
卷 37, 期 17, 页码 4540-4551出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.3699-16.2017
关键词
habituation; learning and memory; rat; sensory filtering; startle; synaptic depression
资金
- Canadian Institutes of Health Research [R4202A08]
- Ontario Mental Health Foundation Postdoctoral Fellowship
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 channels in vivo can 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.
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