title: Modulation of behavior by scaffolding proteins of the post-synaptic density.
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.
authors.affiliation: Jiangsu Key Laboratory of Anesthesiology, Xuzhou Medical College, 209 Tongshan Road, Xuzhou, Jiangsu 221004, China. Electronic address: gaocan@xzmc.edu.cn.
authors.forename: Can
authors.initials: C
authors.lastname: Gao
authors.forename: Natalie C
authors.initials: NC
authors.lastname: Tronson
authors.forename: Jelena
authors.initials: J
authors.lastname: Radulovic
mesh_terms: D000818:Animals; D001921:Brain / Q000502:physiology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D003071:Cognition / Q000502:physiology*; D018390:Gene Targeting; D051528:Guanylate Kinases / Q000235:genetics / Q000378:metabolism*; D000072233:Homer Scaffolding Proteins; D007858:Learning / Q000502:physiology*; D051379:Mice; D057907:Post-Synaptic Density / Q000378:metabolism*; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D000072233:Homer Scaffolding Proteins; D018094:Receptors, Metabotropic Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D051528:Guanylate Kinases
keywords: Behavior; Glutamate receptor; Psychiatric disorders; Scaffold