Circadian rhythms of perineuronal net composition

Harry Pantazopoulos*, Barbara Gisabella, Lindsay Rexrode, David Benefield, Emrah Yildiz, Phoebe Seltzer, Jake Valeri, Gabriele Chelini, Anna Reich, Magdalena Ardelt, Sabina Berretta

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

33 Scopus citations


Perineuronal nets (PNNs) are extracellular matrix (ECM) structures that envelop neurons and regulate synaptic functions. Long thought to be stable structures, PNNs have been recently shown to respond dynamically during learning, potentially regulating the formation of new synapses. We postulated that PNNs vary during sleep, a period of active synaptic modification. Notably, PNN components are cleaved by matrix proteases such as the protease cathepsin-S. This protease is diurnally expressed in the mouse cortex, coinciding with dendritic spine density rhythms. Thus, cathepsin-S may contribute to PNN remodeling during sleep, mediating synaptic reorganization. These studies were designed to test the hypothesis that PNN numbers vary in a diurnal manner in the rodent and human brain, as well as in a circadian manner in the rodent brain, and that these rhythms are disrupted by sleep deprivation. In mice, we observed diurnal and circadian rhythms of PNNs labeled with the lectin Wisteria floribunda agglutinin (WFA+ PNNs) in several brain regions involved in emotional memory processing. Sleep deprivation prevented the daytime decrease of WFA+ PNNs and enhances fear memory extinction. Diurnal rhythms of cathepsin-S expression in microglia were observed in the same brain regions, opposite to PNN rhythms. Finally, incubation of mouse sections with cathepsinS eliminated PNN labeling. In humans, WFA+ PNNsshowedadiurnalrhythmintheamygdalaandthalamicreticular nucleus (TRN). Our results demonstrate that PNNs vary in a circadian manner and this is disrupted by sleep deprivation. We suggest that rhythmic modification of PNNs may contribute to memory consolidation during sleep.

Original languageEnglish (US)
Article numberENEURO.0034-19.2020
Pages (from-to)1-21
Number of pages21
Issue number4
StatePublished - Jul 1 2020
Externally publishedYes


  • Circadian rhythms
  • Extracellular matrix
  • Memory consolidation
  • Perineuronal nets
  • Psychiatric disorders
  • Sleep

ASJC Scopus subject areas

  • Neuroscience(all)


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