Inhibition of Matrix Metalloproteinase 9 Activity Promotes Synaptogenesis in the Hippocampus

Cereb Cortex. 2021 Jul 5;31(8):3804-3819. doi: 10.1093/cercor/bhab050.

Abstract

Information coding in the hippocampus relies on the interplay between various neuronal ensembles. We discovered that the application of a cholinergic agonist, carbachol (Cch), which triggers oscillatory activity in the gamma range, induces the activity of matrix metalloproteinase 9 (MMP-9)-an enzyme necessary for the maintenance of synaptic plasticity. Using electrophysiological recordings in hippocampal organotypic slices, we show that Cch potentiates the frequency of miniature inhibitory and excitatory postsynaptic currents (mIPSCs and mEPSCs, respectively) in CA1 neurons and this effect is MMP-9 dependent. Interestingly, though MMP-9 inhibition prevents the potentiation of inhibitory events, it further boosts the frequency of excitatory mEPSCs. Such enhancement of the frequency of excitatory events is a result of increased synaptogenesis onto CA1 neurons. Thus, the function of MMP-9 in cholinergically induced plasticity in the hippocampus is to maintain the fine-tuned balance between the excitatory and the inhibitory synaptic transmission.

Keywords: MMP-9; carbachol; excitatory; inhibitory; synaptogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CA1 Region, Hippocampal / cytology
  • CA1 Region, Hippocampal / diagnostic imaging
  • Carbachol / pharmacology
  • Cholinergic Agonists / pharmacology
  • Excitatory Postsynaptic Potentials / drug effects
  • Hippocampus / drug effects*
  • Hippocampus / growth & development*
  • Matrix Metalloproteinase 9 / drug effects*
  • Matrix Metalloproteinase Inhibitors / pharmacology*
  • Neurogenesis / drug effects*
  • Neuronal Plasticity / drug effects
  • Patch-Clamp Techniques
  • Rats

Substances

  • Cholinergic Agonists
  • Matrix Metalloproteinase Inhibitors
  • Carbachol
  • Matrix Metalloproteinase 9
  • Mmp9 protein, rat