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      Neuronal MHC Class I Molecules are Involved in Excitatory Synaptic Transmission at the Hippocampal Mossy Fiber Synapses of Marmoset Monkeys

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          Abstract

          Several recent studies suggested a role for neuronal major histocompatibility complex class I (MHCI) molecules in certain forms of synaptic plasticity in the hippocampus of rodents. Here, we report for the first time on the expression pattern and functional properties of MHCI molecules in the hippocampus of a nonhuman primate, the common marmoset monkey ( Callithrix jacchus). We detected a presynaptic, mossy fiber-specific localization of MHCI proteins within the marmoset hippocampus. MHCI molecules were present in the large, VGlut1-positive, mossy fiber terminals, which provide input to CA3 pyramidal neurons. Furthermore, whole-cell recordings of CA3 pyramidal neurons in acute hippocampal slices of the common marmoset demonstrated that application of antibodies which specifically block MHCI proteins caused a significant decrease in the frequency, and a transient increase in the amplitude, of spontaneous excitatory postsynaptic currents (sEPSCs) in CA3 pyramidal neurons. These findings add to previous studies on neuronal MHCI molecules by describing their expression and localization in the primate hippocampus and by implicating them in plasticity-related processes at the mossy fiber–CA3 synapses. In addition, our results suggest significant interspecies differences in the localization of neuronal MHCI molecules in the hippocampus of mice and marmosets, as well as in their potential function in these species.

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          The online version of this article (doi:10.1007/s10571-010-9510-3) contains supplementary material, which is available to authorized users.

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          Autism and abnormal development of brain connectivity.

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            Glial fibrillary acidic protein: GFAP-thirty-one years (1969-2000).

            It is now well established that the glial fibrillary acidic protein (GFAP) is the principal 8-9 nm intermediate filament in mature astrocytes of the central nervous system (CNS). Over a decade ago, the value of GFAP as a prototype antigen in nervous tissue identification and as a standard marker for fundamental and applied research at an interdisciplinary level was recognized (Raine, 135). As a member of the cytoskeletal protein family, GFAP is thought to be important in modulating astrocyte motility and shape by providing structural stability to astrocytic processes. In the CNS of higher vertebrates, following injury, either as a result of trauma, disease, genetic disorders, or chemical insult, astrocytes become reactive and respond in a typical manner, termed astrogliosis. Astrogliosis is characterized by rapid synthesis of GFAP and is demonstrated by increase in protein content or by immunostaining with GFAP antibody. In addition to the major application of GFAP antisera for routine use in astrocyte identification in the CNS, the molecular cloning of the mouse gene in 1985 has opened a new and rich realm for GFAP studies. These include antisense, null mice, and numerous promoter studies. Studies showing that mice lacking GFAP are hypersensitive to cervical spinal cord injury caused by sudden acceleration of the head have provided more direct evidence for a structural role of GFAP. While the structural function of GFAP has become more acceptable, the use of GFAP antibodies and promoters continue to be valuable in studying CNS injury, disease, and development.
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              Neurexins induce differentiation of GABA and glutamate postsynaptic specializations via neuroligins.

              Formation of synaptic connections requires alignment of neurotransmitter receptors on postsynaptic dendrites opposite matching transmitter release sites on presynaptic axons. beta-neurexins and neuroligins form a trans-synaptic link at glutamate synapses. We show here that neurexin alone is sufficient to induce glutamate postsynaptic differentiation in contacting dendrites. Surprisingly, neurexin also induces GABA postsynaptic differentiation. Conversely, neuroligins induce presynaptic differentiation in both glutamate and GABA axons. Whereas neuroligins-1, -3, and -4 localize to glutamate postsynaptic sites, neuroligin-2 localizes primarily to GABA synapses. Direct aggregation of neuroligins reveals a linkage of neuroligin-2 to GABA and glutamate postsynaptic proteins, but the other neuroligins only to glutamate postsynaptic proteins. Furthermore, mislocalized expression of neuroligin-2 disperses postsynaptic proteins and disrupts synaptic transmission. Our findings indicate that the neurexin-neuroligin link is a core component mediating both GABAergic and glutamatergic synaptogenesis, and differences in isoform localization and binding affinities may contribute to appropriate differentiation and specificity.
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                Author and article information

                Contributors
                +49-551-3851-135 , +49-551-3851 307 , aribic@cnl-dpz.de
                Journal
                Cell Mol Neurobiol
                Cellular and Molecular Neurobiology
                Springer US (Boston )
                0272-4340
                1573-6830
                16 March 2010
                16 March 2010
                August 2010
                : 30
                : 6
                : 827-839
                Affiliations
                [1 ]Clinical Neurobiology Laboratory, German Primate Center, Leibniz Institute for Primate Research, Kellnerweg 4, 37077 Göttingen, Germany
                [2 ]Primate Genetics Laboratory, German Primate Center, Leibniz Institute for Primate Research, Göttingen, Germany
                [3 ]Infection Pathology Unit, German Primate Center, Leibniz Institute for Primate Research, Göttingen, Germany
                [4 ]Department of Neurology, Medical School, Georg-August-University, Göttingen, Germany
                [5 ]DFG Research Center Molecular Physiology of the Brain (CMPB), Göttingen, Germany
                [6 ]Laboratory of Molecular Psychiatry, Department of Psychiatry, Westfälische Wilhelms University, Münster, Germany
                [7 ]Institut für Immungenetik, Charité-Universitätsmedizin Berlin, Berlin, Germany
                Article
                9510
                10.1007/s10571-010-9510-3
                2912721
                20232136
                a519c16e-329a-433f-97ba-e7f2db716afc
                © The Author(s) 2010
                History
                : 10 November 2009
                : 1 March 2010
                Categories
                Original Research
                Custom metadata
                © Springer Science+Business Media, LLC 2010

                Neurosciences
                sepsc,vglut1,vgat,neuronal plasticity,psd95,calbindin,ca3,piccolo,vglut 2,gfap
                Neurosciences
                sepsc, vglut1, vgat, neuronal plasticity, psd95, calbindin, ca3, piccolo, vglut 2, gfap

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