Hippocampal signal transmission to the pedunculopontine nucleus and its regulation by dopamine D2 receptors in the nucleus accumbens: an electrophysiological and behavioural study.

The integrative role of the nucleus accumbens and subpallidal area in relaying hippocampal signals to the mesencephalic locomotor region in the brainstem was investigated electrophysiologically in urethan-anaesthetized rats. A behavioural study of the functional connections was also performed in freely moving rats. In the electrophysiological experiments, subpallidal output neurons to the pedunculopontine nucleus and the adjacent ventral gray were first identified by their antidromic responses to electrical stimulation of the pedunculopontine nucleus. Hippocampal stimulation was then shown to inhibit orthodromically some of these subpallidal neurons. The inhibitory response was attenuated following microinjection of a dopamine D2 agonist (LY 171555), but not a D1 agonist (SKF 38393), into the accumbens. This suggests that signal transmission from the hippocampus to the subpallidal output neurons to the pedunculopontine nucleus is modulated by a D2 receptor-mediated mechanism in the nucleus accumbens. Injections of N-methyl-D-aspartate into the ventral subiculum of the hippocampus resulted in a threefold increase in locomotor responses. Injection of a D2 agonist into the accumbens reduced the hyperkinetic response dose-dependently and suggests that D2 receptors regulate locomotor responses initiated by the hippocampal-accumbens pathway. Injection of nipecotic acid, a GABA uptake inhibitor, into the subpallidal area or of procaine, a neural transmission blocker, into the region of the pedunculopontine nucleus, also reduced significantly the hippocampal-induced hyperkinetic response. These results provide evidence of limbic (e.g. hippocampus) influences on locomotor activity by way of nucleus accumbens-subpallidal-pedunculopontine nucleus connections which may contribute to adaptive behaviour. Signal transmission from the hippocampus may be regulated by a dopamine D2 receptor mechanism in the accumbens, presumably mediated by the converging mesolimbic dopaminergic input from the ventral tegmental area.