Modulation of behavior by scaffolding proteins of the post-synaptic density

Can Gao, Natalie C. Tronson, Jelena Radulovic

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

Abstract

Scaffolding proteins of the neuronal post-synaptic density (PSD) are principal organizers of glutamatergic neurotransmission that bring together glutamate receptors and signaling molecules at discrete synaptic locations. Genetic alterations of individual PSD scaffolds therefore disrupt the function of entire multiprotein modules rather than a single glutamatergic mechanism, and thus induce a range of molecular and structural abnormalities in affected neurons. Despite such broad molecular consequences, knockout, knockdown, or knockin of glutamate receptor scaffolds typically affect a subset of specific behaviors and thereby mold and specialize the actions of the ubiquitous glutamatergic neurotransmitter system. Approaches designed to control the function of neuronal scaffolds may therefore have high potential to restore behavioral morbidities and comorbidities in patients with psychiatric disorders. Here we summarize a series of experiments with genetically modified mice revealing the roles of main N-methyl- d-aspartate (NMDA) and group I metabotropic glutamate (mGluR1/5) receptor scaffolds in behavior, discuss the clinical implications of the findings, and propose future research directions.

Original languageEnglish (US)
Pages (from-to)3-12
Number of pages10
JournalNeurobiology of Learning and Memory
Volume105
DOIs
StatePublished - Oct 2013
Externally publishedYes

Keywords

  • Behavior
  • Glutamate receptor
  • Psychiatric disorders
  • Scaffold

ASJC Scopus subject areas

  • Experimental and Cognitive Psychology
  • Cognitive Neuroscience
  • Behavioral Neuroscience

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