Abstract
Cholinergic and non-cholinergic neurons in the brainstem pedunculopontine (PPT) and laterodorsal tegmental (LDT) nuclei innervate diverse forebrain structures. The cholinergic neurons within these regions send heavy projections to thalamic nuclei and provide modulatory input as well to midbrain dopamine cells in the ventral tegmental area (VTA). Cholinergic PPT/LDT neurons are known to send collateralized projections to thalamic and non-thalamic targets, and previous studies have shown that many of the afferents to the VTA arise from neurons that also project to midline and intralaminar thalamic nuclei. However, whether cholinergic projections to the VTA and anterior thalamus (AT) are similarly collateralized is unknown. Ultrastructural work from our laboratory has demonstrated that cholinergic axon varicosities in these regions differ both morphologically and with respect to the expression and localization of the high-affinity choline transporter. We therefore hypothesized that the cholinergic innervation to these regions is provided by separate sets of PPT/LDT neurons. Dual retrograde tract-tracing from the AT and VTA indicated that only a small percentage of the total afferent population to either region showed evidence of providing collateralized input to the other target. Cholinergic and non-cholinergic cells displayed a similarly low percentage of collateralization. These results are contrasted to a control case in which retrograde labeling from the midline paratenial thalamic nucleus and the VTA resulted in higher percentages of cholinergic and non-cholinergic dual-tracer labeled cells. Our results indicate that functionally distinct limbic target regions receive primarily segregated signaling from PPT/LDT neurons.