PREFRONTAL CORTEX INPUTS OF THE NUCLEUS ACCUMBENS-NIGRO-THALAMIC CIRCUIT

The functional organization of the cortico-nucleus accumbens-substanti a nigra pars reticulata circuit was investigated in the rat using comb ined anatomical and electrophysiological approaches. The nucleus accum bens neurons which project to the substantia nigra pars reticulata are located in a circumscribed region of the core immediately adjacent an d extending dorsally to the anterior commissure. As shown by retrograd e and anterograde transports of wheatgerm agglutinin conjugated to hor seradish peroxidase, the region of the nucleus accumbens related to th e substantia nigra was found to receive bilateral inputs from restrict ed areas of the medial and lateral prefrontal cortex, i.e., prelimbic/ medial orbital and dorsal agranular insular areas. The electrical stim ulation of these medial and lateral prefrontal cortical areas induced excitatory responses in nucleus accumbens neurons projecting to the do rsomedial substantia nigra pars reticulata. Interestingly, an importan t proportion (61%) of the nucleus accumbensnigral cells responding to the stimulation of the lateral prefrontal cortex were also excited by the stimulation of the medial prefrontal cortex, demonstrating the exi stence of a convergent influence of these cortical areas on single nuc leus accumbens cells. Furthermore, the present data also show that the stimulation of the medial prefrontal cortex results in a powerful inh ibition of the tonic firing of the substantia nigra pars reticulata ne urons. In conclusion, this study reveals the existence of a functional link between the prefrontal cortex (prelimbic/medial orbital and agra nular insular areas) and the nucleus accumbens neurons which innervate the dorsomedial region of the substantia nigra pars reticulata. Since the dorsomedial region of substantia nigra pars reticulata is known t o project to subfields of the mediodorsal and ventromedial thalamic nu clei related to the prefrontal cortex, the present data further demons trate the existence of a prefrontal-nucleus accumbens-thalamo-cortical circuit involving the substantia nigra pars reticulata.