Neuron
Volume 90, Issue 2, 20 April 2016, Pages 333-347
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Article
Cholinergic Mesopontine Signals Govern Locomotion and Reward through Dissociable Midbrain Pathways

https://doi.org/10.1016/j.neuron.2016.03.028Get rights and content
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Highlights

  • Optogenetic characterization of mesopontine cholinergic cells inputs to midbrain

  • Separable pedunculopontine cholinergic pathways govern locomotion and reward

  • Laterodorsal tegmental cholinergic inputs to VTA modulates reward

  • Retrograde tracing reveals mesopontine cholinergic collateralization to VTA and vSNc

Summary

The mesopontine tegmentum, including the pedunculopontine and laterodorsal tegmental nuclei (PPN and LDT), provides major cholinergic inputs to midbrain and regulates locomotion and reward. To delineate the underlying projection-specific circuit mechanisms, we employed optogenetics to control mesopontine cholinergic neurons at somata and at divergent projections within distinct midbrain areas. Bidirectional manipulation of PPN cholinergic cell bodies exerted opposing effects on locomotor behavior and reinforcement learning. These motor and reward effects were separable via limiting photostimulation to PPN cholinergic terminals in the ventral substantia nigra pars compacta (vSNc) or to the ventral tegmental area (VTA), respectively. LDT cholinergic neurons also form connections with vSNc and VTA neurons; however, although photo-excitation of LDT cholinergic terminals in the VTA caused positive reinforcement, LDT-to-vSNc modulation did not alter locomotion or reward. Therefore, the selective targeting of projection-specific mesopontine cholinergic pathways may offer increased benefit in treating movement and addiction disorders.

Keywords

mesopontine tegmentum
pedunculopontine nucleus
laterodorsal tegmental nucleus
cholinergic neuron
substantia nigra pars compacta
ventral tegmental area
locomotion
conditioned place preference
optogenetics
retrograde tracing

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