title: Glutamate synapses in human cognitive disorders.
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.
authors.affiliation: Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205; email: rhuganir@jhmi.edu.
authors.forename: Lenora
authors.initials: L
authors.lastname: Volk
authors.forename: Shu-Ling
authors.initials: SL
authors.lastname: Chiu
authors.forename: Kamal
authors.initials: K
authors.lastname: Sharma
authors.forename: Richard L
authors.initials: RL
authors.lastname: Huganir
mesh_terms: D000818:Animals; D000067877:Autism Spectrum Disorder / Q000235:genetics / Q000503:physiopathology; D003072:Cognition Disorders / Q000235:genetics* / Q000503:physiopathology*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D018698:Glutamic Acid / Q000502:physiology*; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics / Q000503:physiopathology; D008959:Models, Neurological; D012559:Schizophrenia / Q000235:genetics / Q000503:physiopathology; D013569:Synapses / Q000235:genetics* / Q000502:physiology*
chemical_list: D018698:Glutamic Acid
keywords: autism; excitatory; intellectual disability; neurodevelopmental; plasticity; schizophrenia