The course of neural projection from the prefrontal cortex to the nucleus accumbens in the rat.

Corticostriatal neurons linking the prefrontal cortex and the nucleus accumbens connect the terminal fields of the ascending mesotelencephalic dopamine neurons and may potentially mediate cortical dopaminergic modulation of subcortical dopamine transmission. In our attempt to develop a brain slice preparation that maximally preserves this prefrontal accumbens pathway for in vitro electrophysiological studies, knowledge of the complete course of its projection is critical. Microinjection of biotin-dextran amine as an anterograde tracer into the prefrontal cortex revealed the following in the coronal, sagittal and oblique planes of rat brain. (1) Axonal fibers from the rostral prelimbic cortex projected at an angle of approximately 60 degrees to the horizontal plane through the infralimbic region and mainly entered the rostromedial accumbens. Some also chose a ventral route to enter the "core" of the accumbens. (2) From the central ventral prelimbic regions, axons spread out diffusely and descended to the dorsal accumbens. They then entered throughout the rostral-caudal "shell" of the nucleus accumbens. (3) From the caudal prelimbic region of the prefrontal cortex, axonal fibers descended approximately 10 degrees to the coronal plane and entered the dorsal nucleus accumbens and the caudate nucleus. The denser caudate-projecting fibers gave rise to collaterals that entered the accumbens "core". These results suggest that brain slices that preserve the rostral prelimbic-medial accumbens pathway can be obtained by an oblique (approximately 60 degrees) cut, whereas preservation of the caudal prefrontal-accumbens neurons necessitates a 10 degrees cut. Finally, in whole-cell patch-clamp recordings of accumbens neurons in such slices, orthodromically evoked excitatory postsynaptic potentials to deep layer prefrontal cortical stimulation were observed, thus confirming the functional preservation of portions of this prefrontal cortex nucleus accumbens pathway.