NANOSCALE REMODELING OF GLUTAMATE RECEPTOR ORGANIZATION IN THE CEREBELLUM INDUCED BY CHRONIC STRESS

Chronic stress has been reported to induce changes in synaptic transmission in several brain regions. However, the molecular mechanisms at the synaptic level underlying these changes, particularly in the cerebellum, remain unclear. To address this issue, we generated three types of stress model mice: a social isolation stress model (ISO mice), a restraint stress model (RES mice), and a chronic corticosterone administration model (CORT mice). We then systematically analyzed the expression of over ten postsynaptic proteins, including PSD scaffold proteins and glutamate receptors, in the cerebellum using quantitative immunofluorescence imaging and super-resolution microscopy. The results revealed stress model–specific alterations in postsynaptic protein expression in the cerebellum. In the cerebellar molecular layer, the AMPA receptor subunit GluA1, which is abundantly expressed in Bergmann glia, was markedly reduced in CORT mice. In RES mice, cerebellar GluA1 expression was similarly reduced, although the extent of reduction was smaller than that observed in CORT mice. In contrast, ISO mice showed an opposite pattern, with increased cerebellar GluA1 expression. Notably, cerebellar GluA1 expression levels correlated with the severity of depression-like behavior across mice. These findings indicate that chronic stress induces model-specific alterations in the expression and spatial organization of glutamatergic postsynaptic proteins in the cerebellum, highlighting the diversity of stress effects at the synapse level and providing important insights into the pathophysiology of depression and anxiety disorders.