INSTANTANEOUS PERTURBATION OF DENTATE INTERNEURONAL NETWORKS BY A PRESSURE WAVE-TRANSIENT DELIVERED TO THE NEOCORTEX

Whole-cell patch-clamp recordings and immunocytochemical experiments w ere performed to determine the short- and long-term effects of lateral fluid percussion head injury on the perisomatic inhibitory control of dentate granule cells in the adult rat, with special reference to the development of trauma-induced hyperexcitability. One week after the d elivery of a single, moderate (2.0-2.2 atm) mechanical pressure wave t o the neocortex, the feed-forward inhibitory control of dentate granul e cell discharges was compromised, and the frequency of miniature IPSC s was decreased. Consistent with the electrophysiological data, the nu mber of hilar parvalbumin (PV)- and cholecystokinin (CCK)-positive den tate interneurons supplying the inhibitory innervation of the perisoma tic region of granule cells was decreased weeks and months after head injury. The initial injury to the hilar neurons took place instantaneo usly after the impact and did not require the recruitment of active ph ysiological processes. Furthermore, the decrease in the number of PV- and CCK-positive hilar interneurons was similar to the decrease in the number of the AMPA-type glutamate receptor subunit 2/3-immunoreactive messy cells, indicating that the pressure wave-transient causes injur ious physical stretching and bending of most cells that are large and not tightly packed in a cell layer. These results reveal for the first time that moderate pressure wave-transients, triggered by traumatic h ead injury episodes, impact the dentate neuronal network in a unique t emporal and spatial pattern, resulting in a net decrease in the periso matic control of granule cell discharges.