Pathways from the ventral hippocampus and caudal amygdala to forebrain regions that regulate sensorimotor gating in the rat

Abstract

The neural substrates regulating sensorimotor gating in rodents are studied in order to understand the basis for gating deficits in clinical disorders such as schizophrenia. N-methyl- d-aspartate (NMDA) infusion into the ventral temporal lobe, including caudal parts of the ventral hippocampal region and amygdala, has been shown to disrupt sensorimotor gating in rats, as measured by prepulse inhibition (PPI) of startle. One working model is that reduced PPI after infusion of NMDA into this region is mediated via its efferents to ventral forebrain structures, i.e. medial prefrontal cortex (mPFC) and nucleus accumbens. Yet, PPI-disruptive effects persist after lesions of the precommissural fornix, the principal output pathway of the hippocampal formation. Here, we aimed to characterize non-fornical forebrain projections from this region that might mediate the PPI-disruptive effects of the ventral temporal lobe. Electrolytic lesions of the precommissural fornix in male Sprague–Dawley rats were followed by infusions of fluorogold into the mPFC or by infusions of biotinylated dextan amine into the ventral temporal lobe. Projections from the ventral subiculum and CA1 regions of the ventral hippocampus to the mPFC and accumbens core and shell were interrupted by fornix lesions. Projections to the mPFC and accumbens from other regions of the ventral temporal lobe, particularly the lateral entorhinal cortex and the embedded olfactory and vomeronasal parts of the caudal amygdala, survived fornix lesions. These additional projections coursed rostrally through the amygdala and emerged via the stria terminalis, interstitial nuclei of the posterior limb of the anterior commissure, and the ventral amygdalofugal pathway. PPI-regulatory portions of the ventral temporal lobe innervate the accumbens and mPFC via multiple routes. It remains to be determined which of these non-fornical projections may be responsible for the persistent regulation of PPI after fornix lesions.