ACUTE STRESS RAPIDLY INCREASES THE READILY RELEASABLE POOL OF GLUTAMATE VESICLES IN PREFRONTAL AND FRONTAL CORTEX THROUGH CORTICOSTERONE NON-GENOMIC ACTION

Aims: Several studies suggest a critical role of glutamatergicneurotransmission in the stress response. We compared the effects of acutebehavioural stress with that of in vitroapplication of corticosterone (CORT) to prefrontal/frontal cortex (PFC/FC) synaptosomes,to verify if stress effects on glutamate neurotransmission were mediated by asynaptic action of CORT. Methods: Rats were subjected to acute Footshock (FS)-stress. Synaptosomeswere purified from PFC/FC; glutamate release was measured by superfusion.Electrophysiological experiments were performed on acute PFC slices. Changes invesicle mobilization were measured by Total Internal Reflection FluorescenceMicroscopy (TIRFM). Synapsin I phosphorylation was measured by Western blot. Results: We found that both acute stress and CORT in vitro increase the size of thereadily releasable pool (RRP) of vesicles in PFC/FC synaptosomes. This effectwas abolished by selective mineralocorticoid or glucocorticoid receptor (MR/GR)antagonists. However, CORT did not affect glutamate release evoked bydepolarization and did not alter excitatory transmission in medial PFC slices.We then confirmed, by using TIRFM, that CORT increases vesicle mobilizationtoward the RRP acting on synaptic GR/MR. Finally, we found that both stress andCORT increase the phosphorylation of synapsin I at site 1 in presynapticmembrane. This increase of synapsin I phosphorylation was also found to bedependent on GR/MR and necessary for the increase of RRP. Conclusions: These results suggest that, despite the rapid increaseof RRP size whereby CORT primes synaptic terminals in PFC/FC, the synapticnon-genomic action of CORT is necessary but not sufficient to enhance glutamaterelease.