Developmental regulation of protein interacting with C kinase 1 (PICK1) function in hippocampal synaptic plasticity and learning

Lenora Volk, Chong Hyun Kim, Kogo Takamiya, Yilin Yu, Richard L. Huganir

Research output: Contribution to journalArticle

55 Scopus citations

Abstract

AMPA-type glutamate receptors (AMPARs) mediate the majority of fast excitatory neurotransmission in the mammalian central nervous system. Modulation of AMPAR trafficking supports several forms of synaptic plasticity thought to underlie learning and memory. Protein interacting with C kinase 1 (PICK1) is an AMPAR-binding protein shown to regulate both AMPAR trafficking and synaptic plasticity at many distinct synapses. However, studies examining the requirement for PICK1 in maintaining basal synaptic transmission and regulating synaptic plasticity at hippocampal Schaffer collateral-cornu ammonis 1 (SC-CA1) synapses have produced conflicting results. In addition, the effect of PICK1 manipulation on learningandmemory has not been investigated. In the present study weanalyzed the effect of genetic deletion of PICK1 on basal synaptic transmission and synaptic plasticity at hippocampal Schaffer collateral- CA1 synapses in adult and juvenile mice. Surprisingly, we find that loss of PICK1 has no significant effect on synaptic plasticity in juvenile mice but impairs some forms of long-term potentiation and multiple distinct forms of long-term depression in adult mice. Moreover, inhibitory avoidance learning is impaired only in adultKOmice. These results suggest that PICK1 is selectively required for hippocampal synaptic plasticity and learning in adult rodents.

Original languageEnglish (US)
Pages (from-to)21784-21789
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number50
DOIs
StatePublished - Dec 14 2010

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Keywords

  • AMPA receptor
  • Endocytosis
  • Membrane trafficking
  • Metabotropic glutamate receptor
  • Receptor recycling

ASJC Scopus subject areas

  • General

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