Optogenetic control of dopaminergic neurons’ activity and dopamine release

• Autorzy: Pradel K. , Blasiak T. , Solecki W.
• Języki publikacji: EN

Abstrakty

EN

INTRODUCTION: Dopaminergic (DA) neurons in the ventral tegmental area (VTA) are key players in regulating motivation and learning. Such control is mediated by DA innervation of other brain regions, such as the nucleus accumbens (NAc) and the prefrontal cortex (PFC). AIM(S): With use of optogenetics we aimed to delineate if both electrophysiological activity of DA neurons and DA release in target brain structures follow the optogenetic light stimulation protocols. Additionally, our goal was to compare results obtained with these two approaches. METHOD(S): To address these questions we used genetically modified rats expressing Cre recombinase gene under control of tyrosine hydroxylase gene – a marker of catecholaminergic neurons. Rats were stereotaxically injected into the VTA with adenoviral vectors carrying the Cre-dependent genes for channelrhodopsin-2 (ChR2) and yellow fluorescent protein. After proper expression of ChR2 in DA neurons in vivo electrophysiological or electrochemical experiments (single-unit recordings or fast-scan cyclic voltammetry, respectively) combined with optogenetic stimulation of the VTA were conducted. RESULTS: We demonstrated that laser blue light (473 nm, 5–60 Hz) stimulation alters both the activity of ChR2-expressing TH-positive VTA neurons and DA release in target brain regions. We showed that both DA neuronal firing and DA release elevates not linearly with increasing frequencies of light stimulation. High stimulation frequencies (>20 Hz) decreases both fidelity and amplitude of action potentials, preventing further increase in DA release. Finally, we demonstrated differentiation in DA release within the mesocorticolimbic brain subregions, with higher light-evoked DA concentration in the NAc than in the medial PFC. CONCLUSIONS: ChR2 enables selective control of DA neurons’ activity and subsequent DA release in the target brain regions with high spatial but limited temporal resolution. We demonstrated that light-evoked DA release differ in mesolimbic brain regions. FINANCIAL SUPPORT: This work was supported by the Polish National Science Center (Research grants UMO-2013/11/D/NZ4/02371 and UMO-2014/13/B/ NZ4/00146).

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2017
• Tom: 77
• Numer: Suppl.1
• Opis fizyczny: p.94

Twórcy

autor

Pradel K.

• Institute of Zoology, Jagiellonian University, Department of Neurophysiology and Chronobiology, Cracow, Poland
• Institute of Pharmacology Polish Academy of Sciences, Department of Molecular Neuropharmacology, Cracow, Poland

autor

Blasiak T.

• Institute of Zoology, Jagiellonian University, Department of Neurophysiology and Chronobiology, Cracow, Poland

autor

Solecki W.

• Institute of Pharmacology Polish Academy of Sciences, Department of Molecular Neuropharmacology, Cracow, Poland
• Institute of Applied Psychology, Jagiellonian University, Department of Neurobiology and Neuropsychology, Cracow, Poland