Stroke is a devastating brain disorder. The pathophysiology of stroke is associated with an impaired excitation-inhibition balance in the area that surrounds the infarct core after the insult, the peri-infarct zone. Here we exposed slices from adult mouse prefrontal cortex to oxygen-glucose deprivation and reoxygenation (OGD-RO) to study ischemia-induced changes in the activity of excitatory pyramidal neurons and inhibitory parvalbumin (PV)-positive interneurons. We found that during current-clamp recordings, PV-positive interneurons were more vulnerable to OGD-RO than pyramidal neurons as indicated by the lower percentage of recovery of PV-positive interneurons. However, neither the amplitude of OGD-induced depolarization observed in current-clamp mode nor the OGD-associated current observed in voltage-clamp mode differed between the two cell types. Large amplitude, presumably action-potential dependent, spontaneous postsynaptic inhibitory currents recorded from pyramidal neurons were less frequent after OGD-RO than in control condition. Disynaptic inhibitory postsynaptic currents (dIPSCs) in pyramidal neurons produced predominantly by PV-positive interneurons were reduced by OGD-RO. Following OGD-RO, dendrites of PV-positive interneurons exhibited more pathological beading than those of pyramidal neurons. Our data support the hypothesis that the differential vulnerability to ischemia-like conditions of excitatory and inhibitory neurons leads to the altered excitation-inhibition balance associated with stroke pathophysiology.
Keywords: excitation–inhibition balance; ischemia; oxygen–glucose deprivation; parvalbumin-positive interneurons; prefrontal cortex; pyramidal neurons.
Published by Elsevier Ltd.