Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.04.21.053751v1?rss=1 Authors: Pantazopoulos, H., Gisabella, B., Rexrode, L., Benefield, D., Yildiz, E., Seltzer, P., Valeri, J., Chelini, G., Reich, A., Ardelt, M., Berretta, S. Abstract: 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 may vary during sleep, a period of active synaptic modification. Notably, PNN components are cleaved by matrix proteases such as the protease cathepsin-S, synthesized by microglia. Cathepsin-S is expressed in a diurnal manner in the mouse cortex, coinciding with dendritic spine density rhythms. Thus, cathepsin-S may induce 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, and in a circadian manner in the rodent brain, in association with cathepsin-S expression rhythms coinciding with reported rhythms in synaptic plasticity. 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. 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 cathepsin-S eliminated PNN labeling. In humans, WFA+PNNs showed a diurnal rhythm in the amygdala and thalamic reticular nucleus (TRN). Our results demonstrate that PNNs vary in a circadian manner that coincides with expression rhythms of cathepsin-S in the mouse hippocampus. We suggest that rhythmic modification of PNNs may contribute to memory consolidation during sleep. Copy rights belong to original authors. Visit the link for more info