Optogenetic Stimulation of Frontal D1 Neurons Compensates for Impaired Temporal Control of Action in Dopamine-Depleted Mice

Author(s)

Kim, Young-Cho ; Han, Sang-Woo ; Alberico, Stephanie L. ; Ruggiero, Rafael N. ; De Corte, Benjamin ; Chen, Kuan-Hua ; Narayanan, Nandakumar S.

• Document type: Journal article
• Source: Current Biology; v. 27, n. 1, p. 39-47, JAN 9 2017.
• Web of Science Citations: 24

Abstract

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 MDR 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. (AU)

• FAPESP's process: 14/22817-1 - Modulation of prefrontal cortex activity by optogenetic stimulation of ventral tegmental area during fixed interval task: examining how neuronal firing codes timing
• Grantee: Rafael Naime Ruggiero
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate