期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 115, 期 22, 页码 5792-5797出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1801837115
关键词
lateral habenula; rostromedial tegmental nucleus; motivation; optogenetics; fiber photometry
资金
- Canadian Institutes of Health Research
- Brain & Behavior Research Foundation (National Association for Research on Schizophrenia and Depression Young Investigator Grant)
- NIH [R01-MH091119]
- Shiley-Marcos Endowment
The neural mechanisms conferring reduced motivation, as observed in depressed individuals, is poorly understood. Here, we examine in rodents if reduced motivation to exert effort is controlled by transmission from the lateral habenula (LHb), a nucleus overactive in depressed-like states, to the rostromedial tegmental nucleus (RMTg), a nucleus that inhibits dopaminergic neurons. In an aversive test wherein immobility indicates loss of effort, LHb -> RMTg transmission increased during transitions into immobility, driving LHb -> RMTg increased immobility, and inhibiting LHb -> RMTg produced the opposite effects. In an appetitive test, driving LHb -> RMTg reduced the effort exerted to receive a reward, without affecting the reward's hedonic property. Notably, LHb -> RMTg stimulation only affected specific aspects of these motor tasks, did not affect all motor tasks, and promoted avoidance, indicating that LHb -> RMTg activity does not generally reduce movement but appears to carry a negative valence that reduces effort. These results indicate that LHb -> RMTg activity controls the motivation to exert effort and may contribute to the reduced motivation in depression.
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