Early-life sleep restriction disrupts perineuronal nets and parvalbumin interneuron development in the hippocampus of C57BL/6N mice

Sleep during early life is essential for normal brain development, and its disruption is associated with an increased risk of neurodevelopmental disorders. However, the effects of sleep restriction on the maturation of inhibitory neural circuits remain largely unclear. This study aimed to elucidate how chronic early-life sleep restriction affects the development of hippocampal GABAergic interneurons and perineuronal nets (PNNs), which are critical for learning and memory. C57BL/6N mice were subjected to 3 h of daily sleep restriction from postnatal day (P)10 to P28. Brains were collected at P14, P21, and P28, and hippocampal CA1 and CA3 regions were examined by immunofluorescence staining for GABAergic interneurons (parvalbumin [PV], somatostatin [SOM], calretinin [CR], and GAD67) and PNNs (WFA, AB1031, and Cat-315). The proportion of PV neurons enwrapped by PNNs was also quantified. In the sleep restriction (SR) group, the density of SOM- and GAD67-positive interneurons was transiently reduced at specific time points (SOM at P14; GAD67 at P21) in the CA1 region. In addition, PNN density was significantly decreased at later developmental stages. Furthermore, the proportion of PV neurons enwrapped by PNNs increased in CA1 at P21 but decreased in CA3 at P14. These findings demonstrate that chronic early-life sleep restriction disrupts the normal developmental trajectory of hippocampal inhibitory circuits. In particular, SR induces subtype-specific delays in interneuron maturation and a desynchronization between PV neurons and PNN development. This study suggests that early-life sleep insufficiency may impair mechanisms of synaptic plasticity and neuroprotection, thereby contributing to the risk of neurodevelopmental disorders.