Regulation of sensorimotor gating in rats by hippocampal NMDA: anatomical localization

Prepulse inhibition (PPI) of the startle reflex is a measure of sensorimoto r gating that is reduced in humans with certain neuropsychiatric disorders, including schizophrenia, and in rats after manipulations of limbic cortico -striato-pallido-pontine circuitry. We have reported that PPI is reduced af ter specific manipulations of the hippocampal complex (HPC) in rats, but th e mechanisms for these effects remain poorly understood. For example, dopam inergic substrates clearly regulate PPI, but the PPI-disruptive effects of intra-HPC carbachol or NR IDA are not reversed by D2 receptor antagonists. This study examined the anatomical specificity within the hippocampal compl ex: of the PPI-disruptive effects of NMDA infusion. Startle magnitude and P PT were assessed after acute bilateral infusion of NR;IDA (0, 0.4 or 0.8 mu g) into the dorsal subiculum (DS), region CA1, the ventral subiculum (VS), the rostral entorhinal cortex (ECr) and the caudal entorhinal cortex (ECc). A dorsal-ventral gradient for NMDA effects was observed, with a dose-depen dent disruption of PPI after NMDA infusion into the VS or EC, but not the D S, and with intermediate level effects observed after NMDA infusion into CA 1. A second set of studies confirmed that the failure of NMDA effects in th e DS did not reflect site-related differences in startle magnitude or basel ine levels of PPI. These findings demonstrate the importance of the ventral , but not the dorsal HFC, in the glutamatergic regulation of PPI. (C) 2001 Elsevier Science B.V. All rights reserved.