Neuregulin-1 impairs the long-term depression of hippocampal inhibitory synapses by facilitating the degradation of endocannabinoid 2-AG

Huizhi Du, In Kiu Kwon, Jimok Kim

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

Endocannabinoids play essential roles in synaptic plasticity; thus, their dysfunction often causes impairments in memory or cognition. However, it is not well understood whether deficits in the endocannabinoid system account for the cognitive symptoms of schizophrenia. Here, we show that endocannabinoid-mediated synaptic regulation is impaired by the prolonged elevation of neuregulin-1, the abnormality of which is a hallmark in many patients with schizophrenia. When rat hippocampal slices were chronically treated with neuregulin-1, the degradation of 2-arachidonoylglycerol (2-AG), one of the major endocannabinoids, was enhanced due to the increased expression of its degradative enzyme, monoacylglycerol lipase. As a result, the time course of depolarization-induced 2-AG signaling was shortened, and the magnitude of 2-AG-dependent long-term depression of inhibitory synapses was reduced. Our study reveals that an alteration in the signaling of 2-AG contributes to hippocampal synaptic dysfunction in a hyper-neuregulin-1 condition and thus provides novel insights into potential schizophrenic therapeutics that target the endocannabinoid system.

Original languageEnglish (US)
Pages (from-to)15022-15031
Number of pages10
JournalJournal of Neuroscience
Volume33
Issue number38
DOIs
StatePublished - 2013

ASJC Scopus subject areas

  • Neuroscience(all)

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