ANATOMICAL, ELECTROPHYSIOLOGICAL AND PHARMACOLOGICAL STUDIES OF ASCENDING BRAIN-STEM HIPPOCAMPAL SYNCHRONIZING PATHWAYS

The present review has provided evidence that very potent ascending br ainstem hippocampal synchronizing pathways originate in the rostral pe ns region (RPO and PPT), and ascend to and synapse with several midlin e caudal diencephalic nuclei (posterior hypothalamic and supramammilla ry) which send projections to the medial septal region (MS/vDBB). The medial septal region in turn is a critical nodal point, sending projec tions to limbic structures such as the hippocampal formation, cingulat e cortex, and entorhinal cortex. The pontine and diencephalic nuclei a ppear to play a critical role in determing the translation of increasi ng levels of activation into moment to moment changes in the frequency of hippocampal theta field and theta-related cellular discharges, rel ayed to the MS/vDBB nuclei. The MS/vDBB nuclei appear to play a critic al role in translating increasing levels of ascending synchronizing ac tivation into moment to moment changes in the amplitude of hippocampal theta field activity and the accompanying rate and pattern of phasic theta-ON cells. The MS/vDBB carries out this role through a balance of activity in the septohippocampal cholinergic and GABA-ergic projectio ns. Cholinergic projections provide the afferent excitatory drive for hippocampal theta-ON cells and the GABA-ergic projections act to reduc e the overall level of inhibition by inhibiting hippocampal GABA-ergic interneurons (theta-OFF cells). Both activities must be present for t he generation of hippocampal theta and theta-related cellular activiti es. The balance between the cholinergic and GABA-ergic projections may determine whether hippocampal synchrony (theta) or asynchrony (LIA, l arge amplitude irregular activity) occurs. These same ascending pathwa ys influence the electrophysiological and pharmacological properties o f the neocortex as well. The functional significance of the ascending brainstem synchronizing pathways is the generalized regulation of acti vities in these cortical structures as they relate to sensorimotor beh avior. (C) 1998 Elsevier Science Ltd. All rights reserved.