Incubation of depression: ECM assembly and parvalbumin interneurons after stress

Neurosci Biobehav Rev. 2020 Nov;118:65-79. doi: 10.1016/j.neubiorev.2020.07.015. Epub 2020 Jul 17.


The extracellular space is occupied by a complex network of proteins creating a mesh-like assembly known as the extracellular matrix (ECM). ECM assembles into dense net-like structures, perineuronal nets (PNNs), that envelope cell somas and proximal neurites of predominantly parvalbumin+-(PV+) interneurons. ECM regulates cell-to-cell communication, thereby modulating neuronal network function. Accumulating evidence points to the importance of network dysfunction in the pathophysiology of psychiatric diseases, in which stress acts as a major predisposing factor. Here we review stress-induced changes in ECM/PNNs and PV+-interneurons in preclinical models of (or for) depression, with a special focus on social stress. We argue that the direction of these alterations largely depends on stress recency, as well as on stress timing and the brain region under investigation. A biphasic temporal regulation of ECM/PNNs and PV+-interneuron function is typically observed after stress. Understanding the complex mechanisms underlying ECM organization in relation to stress-induced molecular, cellular and network changes is crucial to further decipher the implications of ECM remodeling in the incubation of depressive symptoms.

Keywords: Chronic mild/unpredictable stress; Early life stress; Experience-dependent plasticity; Hippocampus; Hyper-excitability; Hypo-excitability; Prefrontal cortex; Restraint stress; Social defeat stress.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Depression*
  • Extracellular Matrix
  • Interneurons
  • Neurons
  • Parvalbumins*


  • Parvalbumins