An Essential Role for PICK1 in NMDA Receptor-Dependent Bidirectional Synaptic Plasticity

Akira Terashima, Kenneth A. Pelkey, Jong Cheol Rah, Young Ho Suh, Katherine W. Roche, Graham L L. Collingridge, Chris J. McBain, John T.R. Isaac

Research output: Contribution to journalArticle

115 Citations (Scopus)

Abstract

PICK1 is a calcium-sensing, PDZ domain-containing protein that interacts with GluR2 and GluR3 AMPA receptor (AMPAR) subunits and regulates their trafficking. Although PICK1 has been principally implicated in long-term depression (LTD), PICK1 overexpression in CA1 pyramidal neurons causes a CaMK- and PKC-dependent potentiation of AMPAR-mediated transmission and an increase in synaptic GluR2-lacking AMPARs, mechanisms associated with NMDA receptor (NMDAR)-dependent long-term potentiation (LTP). Here, we directly tested whether PICK1 participates in both hippocampal NMDAR-dependent LTP and LTD. We show that the PICK1 potentiation of AMPAR-mediated transmission is NMDAR dependent and fully occludes LTP. Conversely, blockade of PICK1 PDZ interactions or lack of PICK1 prevents LTP. These observations demonstrate an important role for PICK1 in LTP. In addition, deletion of PICK1 or blockade of PICK1 PDZ binding prevented NMDAR-dependent LTD. Thus, PICK1 plays a critical role in bidirectional NMDAR-dependent long-term synaptic plasticity in the hippocampus.

Original languageEnglish
Pages (from-to)872-882
Number of pages11
JournalNeuron
Volume57
Issue number6
DOIs
StatePublished - 27 Mar 2008

Fingerprint

Neuronal Plasticity
Long-Term Potentiation
N-Methyl-D-Aspartate Receptors
AMPA Receptors
PDZ Domains
Pyramidal Cells
Hippocampus
Calcium
Proteins

Keywords

  • MOLNEURO
  • PROTEINS
  • SIGNALING

Cite this

Terashima, A., Pelkey, K. A., Rah, J. C., Suh, Y. H., Roche, K. W., Collingridge, GL. L., ... Isaac, J. T. R. (2008). An Essential Role for PICK1 in NMDA Receptor-Dependent Bidirectional Synaptic Plasticity. Neuron, 57(6), 872-882. https://doi.org/10.1016/j.neuron.2008.01.028
Terashima, Akira ; Pelkey, Kenneth A. ; Rah, Jong Cheol ; Suh, Young Ho ; Roche, Katherine W. ; Collingridge, Graham L L. ; McBain, Chris J. ; Isaac, John T.R. / An Essential Role for PICK1 in NMDA Receptor-Dependent Bidirectional Synaptic Plasticity. In: Neuron. 2008 ; Vol. 57, No. 6. pp. 872-882.
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Terashima, A, Pelkey, KA, Rah, JC, Suh, YH, Roche, KW, Collingridge, GLL, McBain, CJ & Isaac, JTR 2008, 'An Essential Role for PICK1 in NMDA Receptor-Dependent Bidirectional Synaptic Plasticity', Neuron, vol. 57, no. 6, pp. 872-882. https://doi.org/10.1016/j.neuron.2008.01.028

An Essential Role for PICK1 in NMDA Receptor-Dependent Bidirectional Synaptic Plasticity. / Terashima, Akira; Pelkey, Kenneth A.; Rah, Jong Cheol; Suh, Young Ho; Roche, Katherine W.; Collingridge, Graham L L.; McBain, Chris J.; Isaac, John T.R.

In: Neuron, Vol. 57, No. 6, 27.03.2008, p. 872-882.

Research output: Contribution to journalArticle

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AU - Roche, Katherine W.

AU - Collingridge, Graham L L.

AU - McBain, Chris J.

AU - Isaac, John T.R.

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