HOMEOSTATIC STABILIZATION OF CA3 SYNAPSES FOLLOWING CORTICOSTERONE EXPOSURE

Stress-induced elevations in corticosterone (CORT) modulate hippocampal synaptic function. While acute glucocorticoid signaling can enhance neuronal excitability, chronic exposure is associated with impaired plasticity and cognitive decline. Maintaining synaptic stability is critical in the hippocampal CA3 region, whose dense recurrent circuitry is susceptible to epileptiform activity. Yet, mechanisms conferring resilience to stress-induced synaptic perturbations remain poorly understood. Here, we investigate how CA3 synapses adapt to elevated CORT through homeostatic plasticity mechanisms. We combined whole-cell patch-clamp recordings in acute hippocampal slices with immunolabeling of homeostatic plasticity markers to examine time-dependent effects of CORT on mossy fiber–CA3 synaptic transmission and morphological features. Brief bath application of CORT (20 µM, 15 min) increased frequency and amplitude of spontaneous excitatory synaptic activity while leaving evoked mossy fiber EPSC amplitude and paired-pulse ratio unchanged. These observations suggest enhanced network-driven activity but preserved presynaptic release during acute stress modelled in vitro by brief CORT exposure. Longer exposure produced an apparent compensatory adaptation: incubation with 100 nM CORT for 1 hour modestly increased intrinsic excitability of CA3 pyramidal neurons without altering evoked or spontaneous synaptic transmission. Immunofluorescence analysis of synaptic proteins involved in homeostatic synaptic plasticity following 2-hour incubation with CORT (20 µM) revealed coordinated upregulation of PLK2, Synaptoporin, and VGLUT1 at mossy fiber boutons, consistent with recruitment of homeostatic signaling pathways. Together, these findings suggest that CORT dissociates spontaneous from evoked activity at MF–CA3 synapses while engaging homeostatic effectors that preserve synaptic output under stress, revealing a mechanism that may underlie CA3 circuit resilience.