Focal clusters of peri-synaptic matrix contribute to activity-dependent plasticity and memory in mice

Cell Rep. 2024 May 28;43(5):114112. doi: 10.1016/j.celrep.2024.114112. Epub 2024 Apr 26.

Abstract

Recent findings show that effective integration of novel information in the brain requires coordinated processes of homo- and heterosynaptic plasticity. In this work, we hypothesize that activity-dependent remodeling of the peri-synaptic extracellular matrix (ECM) contributes to these processes. We show that clusters of the peri-synaptic ECM, recognized by CS56 antibody, emerge in response to sensory stimuli, showing temporal and spatial coincidence with dendritic spine plasticity. Using CS56 co-immunoprecipitation of synaptosomal proteins, we identify several molecules involved in Ca2+ signaling, vesicle cycling, and AMPA-receptor exocytosis, thus suggesting a role in long-term potentiation (LTP). Finally, we show that, in the CA1 hippocampal region, the attenuation of CS56 glycoepitopes, through the depletion of versican as one of its main carriers, impairs LTP and object location memory in mice. These findings show that activity-dependent remodeling of the peri-synaptic ECM regulates the induction and consolidation of LTP, contributing to hippocampal-dependent memory.

Keywords: CP: Cell biology; CP: Neuroscience; CS clusters; chondrotin sulfate proteoglycans; extracellular matrix; hippocampus; immunoprecipitation; learning and memory; sensory manipulation; synaptic plasticity; versican.

MeSH terms

  • Animals
  • CA1 Region, Hippocampal / cytology
  • CA1 Region, Hippocampal / metabolism
  • CA1 Region, Hippocampal / physiology
  • Extracellular Matrix* / metabolism
  • Hippocampus / metabolism
  • Hippocampus / physiology
  • Long-Term Potentiation* / physiology
  • Male
  • Memory* / physiology
  • Mice
  • Mice, Inbred C57BL
  • Neuronal Plasticity* / physiology
  • Synapses / metabolism
  • Synapses / physiology