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

Autor(es)

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

• Tipo de documento: Artigo Científico
• Fonte: Current Biology; v. 27, n. 1, p. 39-47, JAN 9 2017.
• Citações Web of Science: 24

Resumo

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)

• Processo FAPESP: 14/22817-1 - Modulação da atividade do córtex pré-frontal por estimulação optogenética da área tegmental ventral durante tarefa de intervalo fixo: examinando como disparos neuronais realizam a codificação temporal
• Beneficiário: Rafael Naime Ruggiero
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado