Cholinergic Mesopontine Signals Govern Locomotion and Reward through Dissociable Midbrain Pathways

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 mesopo...

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Bibliographic Details
Published in:Neuron (Cambridge, Mass.) Mass.), 2016-04, Vol.90 (2), p.333-347
Main Authors: Xiao, Cheng, Cho, Jounhong Ryan, Zhou, Chunyi, Treweek, Jennifer B., Chan, Ken, McKinney, Sheri L., Yang, Bin, Gradinaru, Viviana
Format: Article
Language:English
Subjects:
Anatomy & physiology
Animals
Behavior
cholinergic neuron
Cholinergic Neurons - physiology
conditioned place preference
Histology
laterodorsal tegmental nucleus
locomotion
Locomotion - physiology
Mesencephalon - physiology
mesopontine tegmentum
Neural Pathways - physiology
Neurons
optogenetics
Pars Compacta - physiology
pedunculopontine nucleus
Rats
retrograde tracing
Reward
Rodents
substantia nigra pars compacta
Tegmentum Mesencephali - physiology
ventral tegmental area
Ventral Tegmental Area - physiology
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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. •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 How mesopontine cholinergic signaling fine-tunes the goal-directed behaviors generated by midbrain activity is uncertain. By optogenetically modulating origin-specific cholinergic projections within different midbrain targets, Xiao et al. identify discrete subsets of mesopontine cholinergic neurons that separately regulate locomotion and reward.
ISSN:0896-6273
1097-4199
DOI:10.1016/j.neuron.2016.03.028