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- Title
PICK1 Loss of Function Occludes Homeostatic Synaptic Scaling.
- Authors
Anggono, Victor; Clem, Roger L.; Huganir, Richard L.
- Abstract
Homeostatic synaptic scaling calibrates neuronal excitability by adjusting synaptic strengths during prolonged changes in synaptic activity. The molecular mechanisms that regulate the trafficking of AMPA receptors (AMPARs) during synaptic scaling are largely unknown. Here, we show that chronic activity blockade reduces PICK1 protein level on a time scale that coincides with the accumulation of surface AMPARs. PICK1 loss of function alters the subunit composition and the abundance of GluA2-containing AMPARs. Due to aberrant trafficking of these receptors, the increase in synaptic strength in response to synaptic inactivity is occluded in neurons generated from PICK1 knock-out mouse. In agreement with electrophysiological recordings, no defect of AMPAR trafficking is observed in PICK1 knock-out neurons in response to elevated neuronal activity. Overall, our data reveal an important role of PICK1 in inactivity-induced synaptic scaling by regulating the subunit composition, abundance, and trafficking of GluA2-containing AMPARs.
- Subjects
HOMEOSTASIS; NERVOUS system; NEURONS; CELLS; ELECTROPHYSIOLOGY; ACTIVITIES of daily living
- Publication
Journal of Neuroscience, 2011, Vol 31, Issue 6, p2188
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.5633-10.2011