Functional deficiency of MHC class i enhances LTP and abolishes LTD in the nucleus accumbens of mice Journal Article

Author(s): Edamura, Mitsuhiro; Murakami, Gen; Meng, Hongrui; Itakura, Makoto; Shigemoto, Ryuichi; Fukuda, Atsuo; Nakahara, Daiichiro
Article Title: Functional deficiency of MHC class i enhances LTP and abolishes LTD in the nucleus accumbens of mice
Affiliation IST Austria
Abstract: Major histocompatibility complex class I (MHCI) molecules were recently identified as novel regulators of synaptic plasticity. These molecules are expressed in various brain areas, especially in regions undergoing activity-dependent synaptic plasticity, but their role in the nucleus accumbens (NAc) is unknown. In this study, we investigated the effects of genetic disruption of MHCI function, through deletion of β2-microblobulin, which causes lack of cell surface expression of MHCI. First, we confirmed that MHCI molecules are expressed in the NAc core in wild-type mice. Second, we performed electrophysiological recordings with NAc core slices from wild-type and β2-microglobulin knock-out mice lacking cell surface expression of MHCI. We found that low frequency stimulation induced long-term depression in wild-type but not knock-out mice, whereas high frequency stimulation induced long-term potentiation in both genotypes, with a larger magnitude in knock-out mice. Furthermore, we demonstrated that knock-out mice showed more persistent behavioral sensitization to cocaine, which is a NAc-related behavior. Using this model, we analyzed the density of total AMPA receptors and their subunits GluR1 and GluR2 in the NAc core, by SDS-digested freeze-fracture replica labeling. After repeated cocaine exposure, the density of GluR1 was increased, but there was no change in total AMPA receptors and GluR2 levels in wildtype mice. In contrast, following repeated cocaine exposure, increased densities of total AMPA receptors, GluR1 and GluR2 were observed in knock-out mice. These results indicate that functional deficiency of MHCI enhances synaptic potentiation, induced by electrical and pharmacological stimulation.
Keywords: AMPA receptor; beta 2 microglobulin; cocaine; glutamate receptor 1; glutamate receptor 2; major histocompatibility antigen class 1
Journal Title: PLoS One
Volume: 9
Issue 9
ISSN: 1932-6203
Publisher: Public Library of Science  
Date Published: 2014-09-30
Start Page: Article number e107099
Copyright Statement: CC BY 4.0
Sponsor: This work was supported in part by a Grant-in-Aid for Scientific Research on Innovative Areas (Comprehensive Brain Science Network) and (B) 17330153, from the Ministry of Education, Culture, Sports, Science and Technology of Japan.
DOI: 10.1371/journal.pone.0107099
Notes: We thank Dr. M. Uchijima (Department of Laboratory Medicine, Hamamatsu University School of Medicine), Dr. T. Nagata (Department of Infectious Diseases, Hamamatsu University School of Medicine) for their advice, and Prof. E Molnar (Centre for Synaptic Plasticity, University of Bristol) for pan-AMPA antibody.
Open access: yes (OA journal)