Ketamine modulates spontaneous and miniature excitatory synaptic currents in the medial prefrontal cortex of acutely stressed rats

The cellular and functional changes underlying the adaptive or maladaptive behavioral effects of an acute stressor are not well understood. In the medial prefrontal cortex (mPFC) of preclinical animal models, an acute stressor may rapidly change dendritic morphology and synaptic function. In the male rat mPFC, the foot-shock stress protocol (FS) rapidly (1 hr) increases the number of excitatory synapses, the readily releasable Glu vesicle pool, [K+]-evoked Glu release from synaptosomes (doi.org/10.3389/fpsyt.2015.00060), and the amplitude of spontaneous excitatory postsynaptic currents (sEPSCs) recorded in L2/3 pyramidal neurons (Pyr). Within 24 hrs, FS induces shrinkage of apical dendrites, while no information exists for sEPSCs. Miniature excitatory synaptic currents (mEPSCs) have been suggested to have a neurotrophic and homeostatic role, but the effects of FS on mEPSCs are unknown. To understand the sustained effects of FS on Glu transmission in the mPFC and its regulation by ketamine at antidepressant dosage, synaptic currents were recorded 24 hrs after FS in visually identified layer 2/3 Pyr of prelimbic mPFC in slices from adult male rats. Animals subjected to a 40-min session of inescapable FS (FS group), animals injected with ketamine (10mg/kg) 6 hrs after FS, and controls (CTR) were compared. The amplitude, area, rise, decay, and inter-event intervals of mEPSCs and sEPSCs were analyzed. mEPSCs in the FS group showed minor changes in frequency (small increase) and ampitude (small decrease) vs CTR. Ketamine after FS increased mEPSC frequency and peak amplitude and accelerated rise and decay with no change in area, vs CTR. The above effects were significant with the Kolmogorov-Smirnov test on pooled cumulative unbinned data but not with 2-way ANOVA of binned histograms. sEPSCs frequency in the FS group had a small decrease, with no change in waveform vs. CTR. Ketamine after FS produced similar effects on sESPCs as for mEPSCs. Overall, this work indicates that, 24 hrs after FS, minor changes occur in miniature and spontaneous synaptic currents at layer 2/3 Glu synapses of the mPFC of adult male rats. Ketamine effects on Glu synaptic currents of stressed animals suggest changes in synapse morphology and/or dendritic localization.