--- _id: '1895' abstract: - lang: eng text: 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. acknowledgement: 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. article_number: e107099 author: - first_name: Mitsuhiro full_name: Edamura, Mitsuhiro last_name: Edamura - first_name: Gen full_name: Murakami, Gen last_name: Murakami - first_name: Hongrui full_name: Meng, Hongrui last_name: Meng - first_name: Makoto full_name: Itakura, Makoto last_name: Itakura - first_name: Ryuichi full_name: Shigemoto, Ryuichi id: 499F3ABC-F248-11E8-B48F-1D18A9856A87 last_name: Shigemoto orcid: 0000-0001-8761-9444 - first_name: Atsuo full_name: Fukuda, Atsuo last_name: Fukuda - first_name: Daiichiro full_name: Nakahara, Daiichiro last_name: Nakahara citation: ama: Edamura M, Murakami G, Meng H, et al. Functional deficiency of MHC class i enhances LTP and abolishes LTD in the nucleus accumbens of mice. PLoS One. 2014;9(9). doi:10.1371/journal.pone.0107099 apa: Edamura, M., Murakami, G., Meng, H., Itakura, M., Shigemoto, R., Fukuda, A., & Nakahara, D. (2014). Functional deficiency of MHC class i enhances LTP and abolishes LTD in the nucleus accumbens of mice. PLoS One. Public Library of Science. https://doi.org/10.1371/journal.pone.0107099 chicago: Edamura, Mitsuhiro, Gen Murakami, Hongrui Meng, Makoto Itakura, Ryuichi Shigemoto, Atsuo Fukuda, and Daiichiro Nakahara. “Functional Deficiency of MHC Class i Enhances LTP and Abolishes LTD in the Nucleus Accumbens of Mice.” PLoS One. Public Library of Science, 2014. https://doi.org/10.1371/journal.pone.0107099. ieee: M. Edamura et al., “Functional deficiency of MHC class i enhances LTP and abolishes LTD in the nucleus accumbens of mice,” PLoS One, vol. 9, no. 9. Public Library of Science, 2014. ista: Edamura M, Murakami G, Meng H, Itakura M, Shigemoto R, Fukuda A, Nakahara D. 2014. Functional deficiency of MHC class i enhances LTP and abolishes LTD in the nucleus accumbens of mice. PLoS One. 9(9), e107099. mla: Edamura, Mitsuhiro, et al. “Functional Deficiency of MHC Class i Enhances LTP and Abolishes LTD in the Nucleus Accumbens of Mice.” PLoS One, vol. 9, no. 9, e107099, Public Library of Science, 2014, doi:10.1371/journal.pone.0107099. short: M. Edamura, G. Murakami, H. Meng, M. Itakura, R. Shigemoto, A. Fukuda, D. Nakahara, PLoS One 9 (2014). date_created: 2018-12-11T11:54:35Z date_published: 2014-09-30T00:00:00Z date_updated: 2021-01-12T06:53:54Z day: '30' ddc: - '570' department: - _id: RySh doi: 10.1371/journal.pone.0107099 file: - access_level: open_access checksum: 1f3be936be93114596d61ba44cacee69 content_type: application/pdf creator: system date_created: 2018-12-12T10:09:01Z date_updated: 2020-07-14T12:45:20Z file_id: '4724' file_name: IST-2016-439-v1+1_journal.pone.0107099.pdf file_size: 6262085 relation: main_file file_date_updated: 2020-07-14T12:45:20Z has_accepted_license: '1' intvolume: ' 9' issue: '9' language: - iso: eng month: '09' oa: 1 oa_version: Published Version publication: PLoS One publication_status: published publisher: Public Library of Science publist_id: '5200' pubrep_id: '439' scopus_import: 1 status: public title: Functional deficiency of MHC class i enhances LTP and abolishes LTD in the nucleus accumbens of mice tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4435EBFC-F248-11E8-B48F-1D18A9856A87 volume: 9 year: '2014' ...