Abstract

The nucleus accumbens septi (NAS) receives converging projections from both dopamine (DA) containing neurons of the ventral tegmental area (VTA) and glutamate containing neurons from the ventral subiculum (VS) of the hippocampus. VS projections to the NAS have been suggested to influence investigatory behavior, at least in part, by evoking glutamate-mediated transmitter release from NAS dopaminergic terminals. As the VS is not known to project to the VTA, the possibility that the VS influences dopaminergic transmission at the cell body level has largely been overlooked. In the present thesis, in vivo microdialysis was used to monitor fluctuations in DA release in response to chemical stimulation of the VS by injections of the excitatory amino acid analog N-methyl-D-aspartate (NMDA). Such injections increased investigatory behavior and elevated dopamine in both the DA terminal region of the NAS and the DA cell body region of the VTA. The elevations in VTA DA reflect dendritically released DA and imply an increase in dopaminergic cell firing; this increase was confirmed by single unit recording of identified VTA dopaminergic neurons. VS-evoked elevations in NAS dopamine were blocked by perfusion of the sodium channel blocker tetrodotoxin (TTX) or the ionotropic glutamate receptor antagonist, kynurenic acid (KA) into the VTA. In experiments designed to assess a functional role of VS-mediated elevations in NAS DA, microdialysis was used to monitor elevations in NAS DA evoked by exposure to novel environmental stimuli. Novelty-evoked elevations in NAS DA were abolished by injections of TTX into the VS. Perfusion of KYN into the VTA also blocked novelty-induced elevations in NAS DA. The present experiments indicate that the VS modulates NAS and VTA dopamine. The modulation of NAS dopamine is dependent on, and mediated primarily by, increased impulse flow through the VTA. Although the circuitry through which the VS modulates impulse flow through dopaminergic neurons is not known, it appears to involve a glutamatergic link terminating in the VTA. This circuitry is responsive to environmental stimuli and plays a functional role in the modulation of dopaminergic transmission in response to novelty.