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Neuron-Targeted Caveolin-1 Promotes Ultrastructural and Functional Hippocampal Synaptic Plasticity.


ABSTRACT: 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 (GluN1, GluN2A, and GluN2B). 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 SynCav1. 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.

SUBMITTER: Egawa J 

PROVIDER: S-EPMC6095215 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Neuron-Targeted Caveolin-1 Promotes Ultrastructural and Functional Hippocampal Synaptic Plasticity.

Egawa Junji J   Zemljic-Harpf Alice A   Mandyam Chitra D CD   Niesman Ingrid R IR   Lysenko Larisa V LV   Kleschevnikov Alexander M AM   Roth David M DM   Patel Hemal H HH   Patel Piyush M PM   Head Brian P BP  

Cerebral cortex (New York, N.Y. : 1991) 20180901 9


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  ...[more]

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