Mesolimbic dopamine neurons drive infradian rhythms in sleep-wake and heightened activity state
Authors/Creators
- 1. Douglas Mental Health University Institute
- 2. University of Washington
- 3. McGill University
Description
Infradian mood and sleep-wake rhythms with periods of 48 hr and beyond have been observed in bipolar disorder (BD) subjects that even persist in the absence of exogenous timing cues, indicating an endogenous origin. Here we show that mice exposed to methamphetamine (Meth) in drinking water develop infradian locomotor rhythms with periods of 48 hr and beyond which extend to sleep length and manic state-associated behaviors in support of a model for cycling in BD. The cycling capacity is abrogated upon genetic disruption of dopamine (DA) production in DA neurons of the ventral tegmental area (VTA) or ablation of nucleus accumbens (NAc) projecting DA neurons. Furthermore, chemogenetic activation of VTADA neurons including those that project to the NAc led to locomotor period lengthening in circadian clock-deficient mice, which was counteracted by antipsychotic treatment. Together, our findings argue that BD cycling relies on infradian rhythm generation that depends on mesolimbic DA.
Notes
Funding provided by: National Institutes of Health
ROR ID: https://ror.org/01cwqze88
Award Number: R01-AG062514-03
Funding provided by: National Institutes of Health
ROR ID: https://ror.org/01cwqze88
Award Number: R01-AG067193-02
Funding provided by: Canadian Institutes of Health Research
ROR ID: https://ror.org/01gavpb45
Award Number: PJT-148914
Funding provided by: Canadian Institutes of Health Research
ROR ID: https://ror.org/01gavpb45
Award Number: PJT-487638
Funding provided by: Canadian Institutes of Health Research
ROR ID: https://ror.org/01gavpb45
Award Number: PJT-148790
Funding provided by: Canadian Institutes of Health Research
ROR ID: https://ror.org/01gavpb45
Award Number: PJT-180590
Funding provided by: Canadian Institutes of Health Research
ROR ID: https://ror.org/01gavpb45
Award Number: 201309OG-312343-PT
Funding provided by: Canadian Institutes of Health Research
ROR ID: https://ror.org/01gavpb45
Award Number: 201803PJT-399980-PT
Funding provided by: Natural Sciences and Engineering Research Council
ROR ID: https://ror.org/01h531d29
Award Number: RGPIN-2020-06610
Funding provided by: Natural Sciences and Engineering Research Council
ROR ID: https://ror.org/01h531d29
Award Number: RGPIN-2022-03390
Methods
Unprocessed locomotor activity data recorded from passive infrared sensors. MATLAB scripts to decode this data into a timetable and plot an actogram from this timetable.
Files
README.txt
Additional details
Related works
- Is source of
- 10.5061/dryad.k6djh9wh8 (DOI)