Journal article
Prefrontal D1 dopamine signaling is required for temporal control
Proceedings of the National Academy of Sciences - PNAS, Vol.109(50), pp.20726-20731
12/11/2012
DOI: 10.1073/pnas.1211258109
PMCID: PMC3528521
PMID: 23185016
Abstract
Temporal control, or how organisms guide movements in time to achieve behavioral goals, depends on dopamine signaling. The medial prefrontal cortex controls many goal-directed behaviors and receives dopaminergic input primarily from the midbrain ventral tegmental area. However, this system has never been linked with temporal control. Here, we test the hypothesis that dopaminergic projections from the ventral tegmental area to the prefrontal cortex influence temporal control. Rodents were trained to perform a fixed-interval timing task with an interval of 20 s. We report several results: first, that decreasing dopaminergic neurotransmission using virally mediated RNA interference of tyrosine hydroxylase impaired temporal control, and second that pharmacological disruption of prefrontal D1 dopamine receptors, but not D2 dopamine receptors, impaired temporal control. We then used optogenetics to specifically and selectively manipulate prefrontal neurons expressing D1 dopamine receptors during fixed-interval timing performance. Selective inhibition of D1-expressing prefrontal neurons impaired fixed-interval timing, whereas stimulation made animals more efficient during task performance. These data provide evidence that ventral tegmental dopaminergic projections to the prefrontal cortex influence temporal control via D1 receptors. The results identify a critical circuit for temporal control of behavior that could serve as a target for the treatment of dopaminergic diseases.
Details
- Title: Subtitle
- Prefrontal D1 dopamine signaling is required for temporal control
- Creators
- Nandakumar S Narayanan - Department of Neurology, Carver College of MedicineBenjamin B Land - Department of Psychiatry and Ribicoff Research FacilitiesJohn E Solder - Department of Psychiatry and Ribicoff Research FacilitiesKarl Deisseroth - Departments ofRalph J DiLeone - Department of Psychiatry and Ribicoff Research Facilities
- Resource Type
- Journal article
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, Vol.109(50), pp.20726-20731
- DOI
- 10.1073/pnas.1211258109
- PMID
- 23185016
- PMCID
- PMC3528521
- NLM abbreviation
- Proc Natl Acad Sci U S A
- ISSN
- 0027-8424
- eISSN
- 1091-6490
- Publisher
- National Academy of Sciences
- Alternative title
- Prefrontal dopamine
- Language
- English
- Date published
- 12/11/2012
- Academic Unit
- Neurology; Iowa Neuroscience Institute
- Record Identifier
- 9984020864202771
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