Activity-Dependent Gating of Parvalbumin Interneuron Function by the Perineuronal Net Protein Brevican

Neuron. 2017 Aug 2;95(3):639-655.e10. doi: 10.1016/j.neuron.2017.06.028. Epub 2017 Jul 14.


Activity-dependent neuronal plasticity is a fundamental mechanism through which the nervous system adapts to sensory experience. Several lines of evidence suggest that parvalbumin (PV+) interneurons are essential in this process, but the molecular mechanisms underlying the influence of experience on interneuron plasticity remain poorly understood. Perineuronal nets (PNNs) enwrapping PV+ cells are long-standing candidates for playing such a role, yet their precise contribution has remained elusive. We show that the PNN protein Brevican is a critical regulator of interneuron plasticity. We find that Brevican simultaneously controls cellular and synaptic forms of plasticity in PV+ cells by regulating the localization of potassium channels and AMPA receptors, respectively. By modulating Brevican levels, experience introduces precise molecular and cellular modifications in PV+ cells that are required for learning and memory. These findings uncover a molecular program through which a PNN protein facilitates appropriate behavioral responses to experience by dynamically gating PV+ interneuron function.

Keywords: AMPA receptors; Kv channels; Parvalbumin interneurons; activity-dependent; inhibitory circuitries; learning and memory; perineuronal nets; plasticity; synapse maturation.

MeSH terms

  • Animals
  • Brevican / metabolism*
  • Extracellular Matrix / metabolism
  • GABAergic Neurons / metabolism*
  • Interneurons / metabolism*
  • Memory / physiology*
  • Mice
  • Neuronal Plasticity / physiology
  • Parvalbumins / metabolism*
  • Visual Cortex / metabolism


  • Brevican
  • Parvalbumins