期刊
CEREBRAL CORTEX
卷 28, 期 9, 页码 3255-3266出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/cercor/bhx196
关键词
electron microscopy; long-term potentiation; myelination; ultrastructure; NMDAR
资金
- Veterans Affairs Merit Award from the Department of Veterans Affairs [BX003671, BX000783, BX001963]
- National Institutes of Health, Bethesda, MD, U.S.A. [NS073653, HL091071, HL107200, GM085179, DA034140, AA020098]
- Jerome Lejeune Foundation Grant
A delicate interneuronal communication between pre- and postsynaptic membranes is critical for synaptic plasticity and the formation of memory. Evidence shows that membrane/lipid rafts (MLRs), plasma membrane microdomains enriched in cholesterol and sphingolipids, organize presynaptic proteins and postsynaptic receptors necessary for synaptic formation and signaling. MLRs establish a cell polarity that facilitates transduction of extracellular cues to the intracellular environment. Here we show that neuron-targeted overexpression of an MLR protein, caveolin-1 (SynCav1), in the adult mouse hippocampus increased the number of presynaptic vesicles per bouton, total excitatory type I glutamatergic synapses, number of same-dendrite multiple-synapse boutons, increased myelination, increased long-term potentiation, and increased MLR-localized N-methyl-D-aspartate receptor subunits (G1uN1, G1uN2A, and G1uN2B). Immunogold electron microscopy revealed that Cav-1 localizes to both the pre- and postsynaptic membrane regions as well as in the synaptic cleft. These findings, which are consistent with a significant increase in ultrastructural and functional synaptic plasticity, provide a fundamental framework that underlies previously demonstrated improvements in learning and memory in adult and aged mice by SynCavl. Such observations suggest that Cav-1 and MLRs alter basic aspects of synapse biology that could serve as potential therapeutic targets to promote neuroplasticity and combat neurodegeneration in a number of neurological disorders.
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