Characterization of the extent of pontomesencephalic cholinergic neurons' projections to the thalamus: Comparison with projections to midbrain dopaminergic groups

We sought to determine whether pontomesencephalic cholinergic neurons which we have been shown previously to project to the substantia nigra and ventr al tegmental area also contribute to the thalamic activation projection fro m the pedunculopontine and laterodorsal tegmental nuclei. Retrograde tracin g, immunohistochemical localization of choline acetyltransferase and statis tical methods were used to determine the full extent of the cholinergic pro jection from the pedunculopontine and laterodorsal tegmental nuclei to the thalamus. Progressively larger Fluoro-Gold injections in to the thalamus pr oportionally labeled increasing numbers of pontomesencephalic cholinergic c ells both ipsi- and contralaterally in the pedunculopontine and laterodorsa l tegmental nuclei. Multiple large thalamic injections left only a small fr action of the ipsilateral pontomesencephalic cholinergic group unlabeled. T his small remainder did not correspond to the populations which project to the substantia nigra and ventral tegmental area, thereby indicating that su bstantia nigra- and ventral tegmental area-projecting cholinergic neurons m ust also project to the thalamus. We examined whether there existed any set of cholinergic neurons in the pedunculopontine and laterodorsal tegmental nuclei which did not innervate a thalamic target. The distribution of desce nding projections of the pedunculopontine and laterodorsal tegmental nuclei demonstrated that the unlabeled remainder cannot correspond to a purely de scending group. We also show that substance P-positive cholinergic cells in the laterodorsal tegmental nucleus project to the thalamus. Further studie s demonstrated that the small population of cholinergic cells left unlabele d from the thalamus were the smallest sized cholinergic cells, and included two groups of small, Light-staining cholinergic cells located in the parab rachial area and central gray, adjacent to the main pedunculopontine and la terodorsal tegmental nuclei cholinergic groups. These small cells, in contr ast to thalamic-projecting cholinergic cells, did not stain positively for reduced nicotinamide adenine dinucleotide phosphate-diaphorase. Taken toget her, these results indicated that all of the reduced nicotinamide adenine d inucleotide phosphate diaphorase-positive/choline acetyltransferase-positiv e neurons of the pedunculopontine/laterodorsal tegmental nuclei ascend to i nnervate some portion of the thalamus, in addition to the other targets the y innervate. These findings indicate that the diverse physiological and behavioral effec ts attributed to the activity of pontomesencephalic cholinergic neurons sho uld not be dissociated from their activating effects in the thalamus. (C) 1 999 IBRO. Published by Elsevier Science Ltd.