Incubation of depression: ECM assembly and parvalbumin interneurons after stress

Sabine Spijker*, Maija Kreetta Koskinen, Danai Riga

*Corresponding author for this work

Research output: Contribution to JournalReview articleAcademicpeer-review


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.

Original languageEnglish
Pages (from-to)65-79
Number of pages15
JournalNeuroscience and Biobehavioral Reviews
Publication statusPublished - Nov 2020


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


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