Disrupted mesocortical dopamine contributes to cognitive symptoms of Parkinson's disease (PD). Past work has implicated medial frontal neurons expressing D1 dopamine receptors (D1DRs) in temporal processing. Here, we investigated whether these neurons can compensate for behavioral deficits resulting from midbrain dopamine dysfunction. We report three main results. First, both PD patients and mice with ventral tegmental area (VTA) dopamine depletion had attenuated delta activity (1–4 Hz) in the medial frontal cortex (MFC) during interval timing. Second, we found that optogenetically stimulating MFC D1DR neurons could increase ramping activity among MFC neurons. Finally, stimulating MFC D1DR neurons specifically at delta frequencies (2 Hz) compensated for deficits in temporal control of action caused by VTA dopamine depletion. Our results suggest that cortical networks can be targeted by frequency-specific brain stimulation to improve dopamine-dependent cognitive processing.
Bibliographical noteFunding Information:
This work was funded by the National Institute of Neurological Disorders and Stroke (R01NS078100), the National Institute of Mental Health, NARSAD Young Investigator Grant 22611 from the Brain & Behavior Research Foundation, and grant 2014/22817-1 from the São Paulo Research Foundation (FAPESP).
© 2017 Elsevier Ltd
- dopamine receptors
- interval timing
- mesocortical projections
- prefrontal cortex