image: A. The Dunc13P84200/+ heterozygotes require a greater time to reach 50% loss-of649 righting (T1/2 LOR) reflex levels. (***p<0.001, n = 17). B. The concentration of ethanol was determined in Dunc13P84200/+ and control flies exposed to 50% ethanol vapor for 0, 15, 30, or 45 min; no significant differences were found (p>0.05, n=6). C. The ability of Dunc13P84200/+ and control flies to metabolize ethanol was determined by first exposing flies to ethanol vapor for 45 min, and then by measuring the ethanol remaining in the flies 0, 30, 60, 120 min after the exposure. No significant differences in ethanol metabolism were detected at each time point (t=0.037, p>0.05, n=6). D. The neural expression of the Dunc13KK101383 RNAi transgene led to significantly slower T1/2 LOR compared to the genotype controls (***p<0.05, n = 10). E. The induced neural expression of the Dunc13JF02440 RNAi transgenes also led to a significantly slower T1/2 LOR as compared to the within genotype control (p <0.01, n =8). Induction was accomplished with a 24 hr, 30 °C heat treatment, followed by a 3 hr recovery period at room temperature. F. Inducing the expression of a wild type Munc13-1 cDNA for 48 hrs led to a significant decrease in LOR for the Dunc13P84200/+ flies (***p=0.001, N=9). Induction was accomplished with a 48 hr, 30 °C heat treatment, followed by a 3 hr recovery period at room temperature. G. Munc13-1::EGFP is co-localized with Bruchpilot, a protein localized to presynaptic active zones, in the presynaptic compartment of the larval neural muscular junction. view more
Credit: Xu et al., <i>eNeuro</i> (2018)
Repeated exposure to large quantities of alcohol may lead to tolerance by reducing the activity of a protein that regulates communication between neurons, according to a study of fruit flies published in eNeuro.
Binge drinking has lasting effects on brain activity, but it is not clear how ethanol -- the intoxicating component of alcoholic beverages -- creates these changes. One possibility is that ethanol interacts with a family of proteins (Unc13) that help control the release of neurotransmitters across the synaptic gap between neurons. In mice, worms and flies, mutations affecting Unc13 reduce activity of the cell on the transmitting side of the synapse.
Gregg Roman and colleagues previously found that fruit flies with reduced activity of the gene Dunc13 consumed significantly more ethanol than flies without the mutation. Building on these findings, the researchers now demonstrate that ethanol interferes with the binding of diacylglycerol -- a chemical compound that facilitates neurotransmitter release -- and reduces the activity of the Unc13 protein. Flies with reduced Dunc13 activity took longer to become sedated after being exposed to intoxicating levels of ethanol. The research provides new insight into the neurobiology of alcohol tolerance.
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Article: Ethanol Regulates Presynaptic Activity and Sedation through Presynaptic Unc13 Proteins in Drosophila
DOI: https://doi.org/10.1523/ENEURO.0125-18.2018
Corresponding author: Gregg Roman (University of Mississippi, Oxford, USA), groman@olemiss.edu
About eNeuro
eNeuro, the Society for Neuroscience's open-access journal launched in 2014, publishes rigorous neuroscience research with double-blind peer review that masks the identity of both the authors and reviewers, minimizing the potential for implicit biases. eNeuro is distinguished by a broader scope and balanced perspective achieved by publishing negative results, failure to replicate or replication studies. New research, computational neuroscience, theories and methods are also published.
About The Society for Neuroscience
The Society for Neuroscience is the world's largest organization of scientists and physicians devoted to understanding the brain and nervous system. The nonprofit organization, founded in 1969, now has nearly 37,000 members in more than 90 countries and over 130 chapters worldwide.
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eNeuro