Ketamine alters excitatory synaptic currents in the medial prefrontal cortex of acutely stressed rats

Ketamine alters excitatory synaptic currents in the medial prefrontal cortex of acutely stressed rats E. SCHIAVON1, F. SALERNO SCARZELLA1, L. MUSAZZI2, M. POPOLI2, L. FORTI1. 1Dept. of Biotech. and Life Sci., Univ. of Insubria, Busto Arsizio, Italy; 2Dept. Pharmacol. and Biomolecular Sci., Univ. degli Studi di Milano, Milano, Italy Abstract: 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 male rats, 40 min foot-shock protocol (FS), rapidly (~1 hr) increases the number of excitatory synapses, the readily releasable Glu vesicle pool in synaptosomes, 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 a tendency to 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, as compared to CTR. sEPSCs frequency in the FS group had a tendency to 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, no or minor changes occur in miniature and spontaneous synaptic currents at layer 2/3 excitatory synapses of the mPFC. Ketamine modulation of the Glu synaptic currents of stressed animals suggests changes in synapse morphology and/or dendritic localization.