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Journal article
PSD-95 deficiency alters GABAergic inhibition in the prefrontal cortex
Neuropharmacology, v 179, pp 108277-108277
15 Nov 2020
PMID: 32818520
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Postsynaptic Density Protein-95 (PSD-95) is a major scaffolding protein in the excitatory synapses in the brain and a critical regulator of synaptic maturation for NMDA and AMPA receptors. PSD-95 deficiency has been linked to cognitive and learning deficits implicated in neurodevelopmental disorders such as autism and schizophrenia. Previous studies have shown that PSD-95 deficiency causes a significant reduction in the excitatory response in the hippocampus. However, little is known about whether PSD-95 deficiency will affect gamma-aminobutyric acid (GABA)ergic inhibitory synapses. Using a PSD-95 transgenic mouse model (PSD-95(+/-)), we studied how PSD-95 deficiency affects GABAA receptor expression and function in the medial prefrontal cortex (mPFC) during adolescence. Our results showed a significant increase in the GABAA receptor subunit alpha 1. Correspondingly, there are increases in the frequency and amplitude in spontaneous inhibitory postsynaptic currents (sIPSCs) in pyramidal neurons in the mPFC of PSD-95(+/-) mice, along with a significant increase in evoked IPSCs, leading to a dramatic shift in the excitatory-to-inhibitory balance in PSD-95 deficient mice. Furthermore, PSD-95 deficiency promotes inhibitory synapse function via upregulation and trafficking of NLGN2 and reduced GSK3 beta activity through tyr-216 phosphorylation. Our study provides novel insights on the effects of GABAergic transmission in the mPFC due to PSD-95 deficiency and its potential link with cognitive and learning deficits associated with neuropsychiatric disorders.
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Details
- Title
- PSD-95 deficiency alters GABAergic inhibition in the prefrontal cortex
- Creators
- Erin P. McEachern - Drexel UniversityAustin A. Coley - Drexel UniversitySha-Sha Yang - Drexel UniversityWen-Jun Gao - Drexel University
- Publication Details
- Neuropharmacology, v 179, pp 108277-108277
- Publisher
- Elsevier
- Number of pages
- 8
- Grant note
- F99NS105185 / National Institute of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS) in the U.S.A NIH/NIMH R01MH085666 / National Institute of Health/National Institute of Mental Health in the U.S.A
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy
- Web of Science ID
- WOS:000579725500013
- Scopus ID
- 2-s2.0-85089671997
- Other Identifier
- 991019167579304721
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InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Web of Science research areas
- Neurosciences
- Pharmacology & Pharmacy