Drugs of abuse such as alcohol disrupt the brain’s natural pathways for reward and can lead to addiction. In both mammals and Drosophila, dopamine mediates ethanol-induced hyperactivity, a correlate of ethanol’s rewarding effects. However, the neural circuitry underlying ethanol-induced hyperactivity is largely unknown. Using a group activity tracker coupled with thermogenetic inactivation of dopaminergic neurons (DANs) innervating the mushroom body of the Drosophila brain, we investigated whether distinct populations of DANs are differentially recruited to support ethanol-induced activity in a dose-dependent manner. We found that both the PAM and PPL1 subsets of DANs are involved in the ethanol response and have ethanol-dependent modulatory activity. Additionally, we discovered neuronal subsets with dynamic roles in modulating ethanol-induced activity as well as subsets not involved in the ethanol response. Importantly, we found increased DAN involvement at higher doses of ethanol, suggesting that more DANs are recruited at higher doses to counter the sedating effects of ethanol. Overall, this study clarifies our understanding of the dose-dependent activity of specific subsets of DANs and can serve as a starting point for more detailed circuit analyses.
Song, Sophia,
"Neural circuits for low and moderate alcohol responses in Drosophila melanogaster"
(2019).
Neuroscience Theses and Dissertations.
Brown Digital Repository. Brown University Library.
https://doi.org/10.26300/ewpn-s205
