A comparison of ventral tegmental neurons projecting to optic flow regions of the inferior olive vs. the hippocampal formation

The ventral tegmental area (catecholaminergic group A10) is a midbrain region characterized by concentrated dopaminergic immunoreactivity. Previous studies in pigeons show that the ventral tegmental area provides a robust projection to the hippocampal formation and to the medial column of the inferior olive. However, the distribution, morphology, and neurochemical content of the neurons that constitute these projections have not been resolved. In this study, we used a combination of retrograde tracing techniques and immunofluorohistochemistry to address these issues. Retrograde tracers were used to demonstrate that the distribution of ventral tegmental area neurons projecting to the hippocampus and the inferior olive overlap in the caudo-ventral ventral tegmental area. The hippocampus- and inferior olive-projecting ventral tegmental area neurons could not be distinguished based on morphology: most neurons had small- to medium-sized multipolar or fusiform soma. Double-labeling with fluorescent retrograde tracers revealed that the hippocampus- and medial column of the inferior olive-projecting neurons were found intermingled in the ventral tegmental area, but no cells were double labeled; i.e. individual ventral tegmental area neurons do not project to both the hippocampal formation and medial column of the inferior olive. Finally, we found that a minority (8.2%) of ventral tegmental area neurons providing input to the hippocampus were tyrosine hydroxylase-immunoreactive, whereas none of the inferior olive-projecting neurons were tyrosine hydroxylase positive. Combined, our findings show that the projections to the hippocampus and olivocerebellar pathway arise from intermixed subpopulations of ventral tegmental area neurons with indistinguishable morphology but only the hippocampal projection involves dopaminergic neurons. We suggest that equivalent projections from the ventral tegmental area to the hippocampal formation and inferior olive exist in mammals and discuss their potential role in the processing of optic flow and the analysis of self-motion.