Journal
NEURON
Volume 90, Issue 2, Pages 333-347Publisher
CELL PRESS
DOI: 10.1016/j.neuron.2016.03.028
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Funding
- NIH [IDP20D017782-1, BRAIN 1U01NS090577]
- PECASE
- NIH/NIA [1R01AG047664-01]
- Heritage Medical Research Institute
- Pew Charitable Trust
- Michael J. Fox Foundation
- Sloan Foundation
- Beckman Institute for the Resource Center on CLARITY, Optogenetics, and Vector Engineering for technology development and broad dissemination
- NIH/NIMH [1R21MH103824-01]
- Kimmel Foundation
- Human Frontiers in Science Program
- Mallinckrodt Foundation
- Gordon and Betty Moore Foundation [GBMF2809]
- Caltech-GIST
- Caltech-CBEA
- Caltech-CEMI
- Caltech-City of Hope Biomedical Initiative
- NIH Predoctoral Training in Biology and Chemistry [2T32GM007616-36]
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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 photoexcitation 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.
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