The rat striatum: a target nucleus for ascending axon collaterals of the entopedunculo-habenular pathway

Direct projections from the entopeduncular nucleus (Ep) to the striatum were examined in the rat using retrograde tracing techniques. After injecting horseradish peroxidase (HRP) into the caudoputamen (CPU), labeled fibers could be traced medially to go through and/or terminate in both the globus pallidus (GP) and Ep ipsilateral to the injection. Interestingly, HRP-positive neuronal perikarya were observed in the Ep as well as in the GP after the CPU injections. These labeled Ep neurons were medium in size and restricted to the rostral 1/3 of the nucleus, in a distribution which overlapped the terminal fields from the CPU. A fluorescent tracer injection into the CPU resulted in retrograde labeling of Ep cells in the same fashion as after HRP injections. A second experiment was designed to determine whether the Ep cells projecting to the CPU have axon collaterals to any of the other known terminal fields of the Ep. Following True blue (TB) injections into the CPU and Diamidino yellow (DY) injections into the lateral habenular nucleus (lHb), all the TB-positive neurons in the rostral 1/3 of the Ep were unequivocally double-labeled with DY. On the other hand, the TB-labeled Ep neurons were never double labeled with DY injected into the centre median-parafascicular complex (CM-Pf) or ventroanterior-ventrolateral complex (VA-VL) of the thalamus or nucleus tegmenti pedunculopontinus pars compacta (TPC). The present study shows that single Ep neurons in the rostral 1/3 of the nucleus innervate both the striatum and lHb, and raises the possibility that these neurons may have a critical role in integrating motor and limbic functions in the basal ganglia.