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

Cereb Cortex. 2018 Sep 1;28(9):3255-3266. doi: 10.1093/cercor/bhx196.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Caveolin 1 / metabolism*
  • Hippocampus / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Neuronal Plasticity / physiology*
  • Neurons / physiology*


  • Caveolin 1