학술논문

Genetic inhibition of neurotransmission reveals role of glutamatergic input to dopamine neurons in high-effort behavior
Document Type
article
Source
Molecular Psychiatry. 23(5)
Subject
Biological Psychology
Pharmacology and Pharmaceutical Sciences
Biomedical and Clinical Sciences
Psychology
Basic Behavioral and Social Science
Behavioral and Social Science
Neurosciences
Drug Abuse (NIDA only)
Substance Misuse
Underpinning research
1.1 Normal biological development and functioning
Aetiology
2.1 Biological and endogenous factors
Neurological
Good Health and Well Being
Animals
Dopamine
Dopaminergic Neurons
Excitatory Amino Acid Agents
Learning
Male
Mesencephalon
Mice
Mice
Transgenic
Motivation
Reward
Synaptic Transmission
Biological Sciences
Medical and Health Sciences
Psychology and Cognitive Sciences
Psychiatry
Clinical sciences
Biological psychology
Clinical and health psychology
Language
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.