Selective Activation of Cholinergic Interneurons Enhances Accumbal Phasic Dopamine Release: Setting the Tone for Reward Processing
Roger Cachope,
Yolanda Mateo,
Brian N. Mathur,
James Irving,
Hui-Ling Wang,
Marisela Morales,
David M. Lovinger,
Joseph F. Cheer
Affiliations
Roger Cachope
Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA
Yolanda Mateo
Section on Synaptic Pharmacology, Laboratory for Integrative Neuroscience, National Institute on Alcohol Abuse and Alcoholism, U.S. National Institutes of Health, Rockville, MD 20892, USA
Brian N. Mathur
Section on Synaptic Pharmacology, Laboratory for Integrative Neuroscience, National Institute on Alcohol Abuse and Alcoholism, U.S. National Institutes of Health, Rockville, MD 20892, USA
James Irving
Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA
Hui-Ling Wang
National Institute on Drug Abuse, U.S. National Institutes of Health, Baltimore, MD 21224, USA
Marisela Morales
National Institute on Drug Abuse, U.S. National Institutes of Health, Baltimore, MD 21224, USA
David M. Lovinger
Section on Synaptic Pharmacology, Laboratory for Integrative Neuroscience, National Institute on Alcohol Abuse and Alcoholism, U.S. National Institutes of Health, Rockville, MD 20892, USA
Joseph F. Cheer
Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA
Dopamine plays a critical role in motor control, addiction, and reward-seeking behaviors, and its release dynamics have traditionally been linked to changes in midbrain dopamine neuron activity. Here, we report that selective endogenous cholinergic activation achieved via in vitro optogenetic stimulation of nucleus accumbens, a terminal field of dopaminergic neurons, elicits real-time dopamine release. This mechanism occurs via direct actions on dopamine terminals, does not require changes in neuron firing within the midbrain, and is dependent on glutamatergic receptor activity. More importantly, we demonstrate that in vivo selective activation of cholinergic interneurons is sufficient to elicit dopamine release in the nucleus accumbens. Therefore, the control of accumbal extracellular dopamine levels by endogenous cholinergic activity results from a complex convergence of neurotransmitter/neuromodulator systems that may ultimately synergize to drive motivated behavior.
