INDUCTION OF FOS-PROTEIN IN THE FOREBRAIN AND DISRUPTION OF SENSORIMOTOR GATING FOLLOWING N-METHYL-D-ASPARTATE INFUSION INTO THE VENTRAL HIPPOCAMPUS OF THE RAT

Several neuropsychiatric disorders, including schizophrenia, are chara cterized by sensorimotor gating deficits. Prepulse inhibition of the a coustic startle response is an operational measure assessing sensorimo tor gating and has been found to be reduced in schizophrenic patients. Much attention has therefore been paid to the neuronal mechanisms und erlying the disruption of prepulse inhibition. The activity of limbic forebrain structures such as the septohippocampal system, the prefront al cortex, and the nucleus accumbens has been the main focus of recent research into the regulation of prepulse inhibition in rats. We here provide a functional anatomical picture of forebrain structures probab ly involved in the regulation of prepulse inhibition. Stimulation of t he ventral hippocampus with a subconvulsive dose of N-methyl-D-asparta te caused a significant and long-lasting disruption of prepulse inhibi tion. Immunostaining of the c-Fos protein revealed a characteristic pa ttern of neuronal activity in various forebrain areas, including the n ucleus accumbens and different frontal cortical areas after hippocampa l stimulation. Based on the present findings, we conclude that the ove ractivity within a network of cortico-limbic forebrain structures comp romises the normal processing of sensory stimuli by disrupting a neuro nal filter mechanism. Interestingly, there is a considerable overlap b etween the pattern of neuronal activity observed in our study and the brain pathology in schizophrenics reported in the literature. (C) 1998 IBRO. Published by Elsevier Science Ltd.