title: Genetic inhibition of neurotransmission reveals role of glutamatergic input to dopamine neurons in high-effort behavior.
abstract: Midbrain dopamine neurons are crucial for many behavioral and cognitive functions. As the major excitatory input, glutamatergic afferents are important for control of the activity and plasticity of dopamine neurons. However, the role of glutamatergic input as a whole onto dopamine neurons remains unclear. Here we developed a mouse line in which glutamatergic inputs onto dopamine neurons are specifically impaired, and utilized this genetic model to directly test the role of glutamatergic inputs in dopamine-related functions. We found that while motor coordination and reward learning were largely unchanged, these animals showed prominent deficits in effort-related behavioral tasks. These results provide genetic evidence that glutamatergic transmission onto dopaminergic neurons underlies incentive motivation, a willingness to exert high levels of effort to obtain reinforcers, and have important implications for understanding the normal function of the midbrain dopamine system.
authors.affiliation: Synapse and Neural Circuit Research Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Hutchison
authors.affiliation: Synapse and Neural Circuit Research Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
authors.forename: X
authors.initials: X
authors.lastname: Gu
authors.affiliation: National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA.
authors.forename: M F
authors.initials: MF
authors.lastname: Adrover
authors.affiliation: Synapse and Neural Circuit Research Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
authors.forename: M R
authors.initials: MR
authors.lastname: Lee
authors.affiliation: Department of Neurosciences, University of California San Diego, La Jolla, CA, USA.
authors.forename: T S
authors.initials: TS
authors.lastname: Hnasko
authors.affiliation: National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA.
authors.forename: V A
authors.initials: VA
authors.lastname: Alvarez
authors.affiliation: Synapse and Neural Circuit Research Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
authors.forename: W
authors.initials: W
authors.lastname: Lu
mesh_terms: D000818:Animals; D004298:Dopamine / Q000502:physiology; D059290:Dopaminergic Neurons / Q000378:metabolism* / Q000502:physiology*; D018683:Excitatory Amino Acid Agents / Q000378:metabolism*; D007858:Learning / Q000502:physiology; D008297:Male; D008636:Mesencephalon / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009042:Motivation; D012201:Reward; D009435:Synaptic Transmission / Q000235:genetics / Q000502:physiology
chemical_list: D018683:Excitatory Amino Acid Agents; D004298:Dopamine