Abstract
Many central synapses are highly sensitive to alcohol, and it is now accepted that short-term alterations in synaptic function may lead to longer-term changes in circuit function. The regulation of postsynaptic receptors by alcohol has been well studied, but the mechanisms underlying the effects of alcohol on the presynaptic terminal are relatively unexplored. To identify a pathway by which alcohol regulates neurotransmitter release, we recently investigated the mechanism by which ethanol induces Vamp2, but not Vamp1, in mouse primary cortical cultures. These two genes encode isoforms of synaptobrevin, a vesicular soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) protein required for synaptic vesicle fusion. We found that alcohol activates the transcription factor heat shock factor 1 (HSF1) to induce Vamp2 expression, while Vamp1 mRNA levels remain unaffected. As the Vamp2 gene encodes a SNARE protein, we then investigated whether ethanol exposure and HSF1 transcriptional activity alter neurotransmitter release using electrophysiology. We found that alcohol increased the frequency of γ-aminobutyric acid (GABA)-mediated miniature IPSCs via HSF1, but had no effect on mEPSCs. Overall, these data indicate that alcohol induces HSF1 transcriptional activity to trigger a specific coordinated adaptation in GABAergic presynaptic terminals. This mechanism could explain some of the changes in synaptic function that occur soon after alcohol exposure, and may underlie some of the more enduring effects of chronic alcohol intake on local circuit function.
Highlights
Alcohol abuse and dependence is a major global health problem, but little is understood about the neuroadaptations that underlie the development of this disease
We have found that a subset of genes encoding sensitive factor attachment protein receptor (SNARE) and SNARE-associated proteins are induced by acute alcohol exposure, including synaptotagmin 1 (Syt1), Vamp2, and Snap25 (Varodayan et al, 2011)
The ethanol effect on Vamp2 gene expression showed a halfmaximal activation at 40 ± 6 mM (33 ± 4% increase compared with ethanol-naïve control) and saturated at 80 mM (57 ± 5% increase)
Summary
Alcohol abuse and dependence is a major global health problem, but little is understood about the neuroadaptations that underlie the development of this disease. MIPSC frequency is increased in the VTA of mice administered a single ethanol dose one day prior to recording (Melis et al, 2002) and in the CeA of chronically ethanol-treated rats (Roberto et al, 2004). Despite these findings that alcohol increases GABA release, the effects of alcohol on synaptic vesicle fusion machinery are not well understood
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
