title: Functional deficiency of MHC class I enhances LTP and abolishes LTD in the nucleus accumbens of mice.
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 wild-type 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.
authors.affiliation: Division of Psychology and Behavioral Neuroscience, Department of Integrated Human Sciences, Hamamatsu University School of Medicine, Higashi-ku, Hamamatsu, Japan.
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Edamura
authors.affiliation: Division of Psychology and Behavioral Neuroscience, Department of Integrated Human Sciences, Hamamatsu University School of Medicine, Higashi-ku, Hamamatsu, Japan.
authors.forename: Gen
authors.initials: G
authors.lastname: Murakami
authors.affiliation: Division of Psychology and Behavioral Neuroscience, Department of Integrated Human Sciences, Hamamatsu University School of Medicine, Higashi-ku, Hamamatsu, Japan.
authors.forename: Hongrui
authors.initials: H
authors.lastname: Meng
authors.affiliation: Department of Biochemistry, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Itakura
authors.affiliation: Division of Cerebral Structure, National Institute for Physiological Sciences, Myodaiji, Okazaki, Japan; Institute of Science and Technology Austria, Klosterneuburg, Austria.
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Shigemoto
authors.affiliation: Department of Neurophysiology, Hamamatsu University School of Medicine, Higashi-ku, Hamamatsu, Japan.
authors.forename: Atsuo
authors.initials: A
authors.lastname: Fukuda
authors.affiliation: Division of Psychology and Behavioral Neuroscience, Department of Integrated Human Sciences, Hamamatsu University School of Medicine, Higashi-ku, Hamamatsu, Japan.
authors.forename: Daiichiro
authors.initials: D
authors.lastname: Nakahara
mesh_terms: D000818:Animals; D019706:Excitatory Postsynaptic Potentials; D015395:Histocompatibility Antigens Class I / Q000235:genetics* / Q000378:metabolism; D017774:Long-Term Potentiation; D036881:Long-Term Synaptic Depression; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009473:Neuronal Plasticity; D009714:Nucleus Accumbens / Q000378:metabolism / Q000503:physiopathology*; D018091:Receptors, AMPA / Q000378:metabolism
chemical_list: D015395:Histocompatibility Antigens Class I; D018091:Receptors, AMPA