Glutamate Synapses in Human Cognitive Disorders

Lenora Volk, Shu Ling Chiu, Kamal Sharma, Richard L. Huganir

Research output: Contribution to journalArticle

Abstract

Accumulating data, including those from large genetic association studies, indicate that alterations in glutamatergic synapse structure and function represent a common underlying pathology in many symptomatically distinct cognitive disorders. In this review, we discuss evidence from human genetic studies and data from animal models supporting a role for aberrant glutamatergic synapse function in the etiology of intellectual disability (ID), autism spectrum disorder (ASD), and schizophrenia (SCZ), neurodevelopmental disorders that comprise a significant proportion of human cognitive disease and exact a substantial financial and social burden. The varied manifestations of impaired perceptual processing, executive function, social interaction, communication, and/or intellectual ability in ID, ASD, and SCZ appear to emerge from altered neural microstructure, function, and/or wiring rather than gross changes in neuron number or morphology. Here, we review evidence that these disorders may share a common underlying neuropathy: altered excitatory synapse function. We focus on the most promising candidate genes affecting glutamatergic synapse function, highlighting the likely disease-relevant functional consequences of each. We first present a brief overview of glutamatergic synapses and then explore the genetic and phenotypic evidence for altered glutamate signaling in ID, ASD, and SCZ.

Original languageEnglish (US)
Pages (from-to)127-149
Number of pages23
JournalAnnual review of neuroscience
Volume38
DOIs
StatePublished - Jul 8 2015

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Keywords

  • Autism
  • Excitatory
  • Intellectual disability
  • Neurodevelopmental
  • Plasticity
  • Schizophrenia

ASJC Scopus subject areas

  • Neuroscience(all)

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