Selective depolarization of interneurons in the early posttraumatic dentate gyrus: Involvement of the Na+/K+-ATPase

Interneurons innervating dentate granule cells are potent regulators of the entorhino-hippocampal interplay. Traumatic brain injury, a leading cause o f death and disability among young adults, is frequently associated with ra pid neuropathological changes, seizures, and short-term memory deficits bot h in humans and experimental animals, indicating significant posttraumatic perturbations of hippocampal circuits. To determine the pathophysiological alterations that affect the posttraumatic functions of dentate neuronal net works within the important early (hours to days) posttraumatic period, whol e cell patch-clamp recordings were performed from granule cells and interne urons situated in the granule cell layer of the dentate gyrus of head-injur ed and age-matched, sham-operated control rats. The data show that a single pressure wave-transient delivered to the neocortex of rats (mimicking mode rate concussive head trauma) resulted in a characteristic (similar to 10 mV ), transient (<4 days), selective depolarizing shift in the resting membran e potential of dentate interneurons, but not in neighboring granule cells. The depolarization was not associated with significant changes in action po tential characteristics or input resistance, and persisted in the presence of antagonists of ionotropic and metabotropic glutamate, and GABA(A) and mu scarinic receptors, as well as blockers of voltage-dependent sodium channel s and of the h-current. The differential action of the cardiac glycosides o ubain and stophanthidin on interneurons from control versus head-injured ra ts indicated that the depolarization of interneurons was related to the tra uma-induced decrease in the activity of the electrogenic Na+/K+-ATPase. In contrast, the Na+/K+-ATPase activity in granule cells did not change. Intra cellular injection of Na+, Ca2+-chelator and ATP, as well as ATP alone, abo lished the difference between the resting membrane potentials of control an d injured interneurons. The selective posttraumatic depolarization increase d spontaneous firing in interneurons, enhanced the frequency and amplitude of spontaneous inhibitory postsynaptic currents (IPSCs) in granule cells, a nd augmented the efficacy of depolarizing inputs to discharge interneurons. These results demonstrate that mechanical neurotrauma delivered to a remot e site has highly selective effects on different cell types even within the same cell layer, and that the electrogenic Na+-pump plays a role in settin g the excitability of hippocampal interneuronal networks after injury.