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 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.
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
Cheng
C
Xiao
Computation and Neural Systems, California Institute of Technology, Pasadena, CA 91125, USA.
Jounhong Ryan
JR
Cho
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
Chunyi
C
Zhou
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
Jennifer B
JB
Treweek
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
Ken
K
Chan
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
Sheri L
SL
McKinney
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
Bin
B
Yang
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA. Electronic address: viviana@caltech.edu.
Viviana
V
Gradinaru
D000818:Animals; D059329:Cholinergic Neurons / Q000502:physiology*; D008124:Locomotion / Q000502:physiology*; D008636:Mesencephalon / Q000502:physiology*; D009434:Neural Pathways / Q000502:physiology*; D065842:Pars Compacta / Q000502:physiology; D051381:Rats; D012201:Reward; D013681:Tegmentum Mesencephali / Q000502:physiology*; D017557:Ventral Tegmental Area / Q000502:physiology
cholinergic neuron; conditioned place preference; laterodorsal tegmental nucleus; locomotion; mesopontine tegmentum; optogenetics; pedunculopontine nucleus; retrograde tracing; substantia nigra pars compacta; ventral tegmental area