Current Biology
Volume 27, Issue 1, 9 January 2017, Pages 39-47
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Article
Optogenetic Stimulation of Frontal D1 Neurons Compensates for Impaired Temporal Control of Action in Dopamine-Depleted Mice

https://doi.org/10.1016/j.cub.2016.11.029Get rights and content
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Highlights

  • Humans and mice have dopamine-dependent delta rhythms in medial frontal cortex

  • Stimulating medial frontal neurons expressing D1DRs improves temporal processing

  • Delta stimulation of medial frontal neurons at 2 Hz can improve interval timing

Summary

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.

Keywords

prefrontal cortex
interval timing
dopamine receptors
mesocortical projections
optogenetics

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