Circadian Rhythms of Perineuronal Net Composition

Area of Science:

• Neuroscience
• Extracellular Matrix Biology
• Chronobiology

Background:

• Perineuronal nets (PNNs) are extracellular matrix structures regulating neuronal function.
• PNNs were previously considered stable but are now known to change dynamically during learning.
• Sleep is a critical period for synaptic modification, suggesting PNNs may also change during sleep.

Purpose of the Study:

• To investigate diurnal and circadian rhythms of PNNs in rodent and human brains.
• To determine if sleep deprivation disrupts PNN rhythms.
• To explore the role of cathepsin-S in PNN remodeling during sleep.

Main Methods:

• Quantification of Wisteria floribunda agglutinin (WFA+) labeled PNNs in mouse and human brain regions.
• Assessment of PNN rhythms under normal and sleep-deprived conditions in mice.
• Measurement of cathepsin-S expression in microglia.
• In vitro incubation of brain sections with cathepsin-S.

Main Results:

• Diurnal and circadian rhythms of WFA+ PNNs were observed in mouse brain regions involved in emotional memory.
• Sleep deprivation abolished the daytime decrease in WFA+ PNNs and enhanced fear memory extinction.
• Cathepsin-S expression in microglia showed diurnal rhythms opposite to PNN rhythms.
• Cathepsin-S treatment degraded PNN labeling in mouse brain sections.
• Diurnal rhythms of WFA+ PNNs were found in the human amygdala and thalamic reticular nucleus (TRN).

Conclusions:

• PNNs exhibit circadian rhythms in the brain, which are disrupted by sleep deprivation.
• Rhythmic PNN modification, potentially mediated by cathepsin-S, may play a role in memory consolidation during sleep.
• These findings highlight the dynamic nature of PNNs and their involvement in sleep-dependent memory processes.