Background
Inbred mouse strains are differentially sensitive to the acute effects of ethanol and are useful tools for examining how unique genomes differentially affect alcohol-related behaviors and physiology. DBA/2J mice have been shown to be sensitive to the acute anxiolytic effects of alcohol as well as the anxiogenic effects of withdrawal from chronic alcohol exposure, while B6 mice are resistant to both. Considering that the basolateral amygdala is an important brain region for the acute and chronic effects of ethanol on fear and anxiety related behaviors, we hypothesized that there would be strain-dependent differences in the acute effects of ethanol in BLA slices.
Methods
We utilized patch clamp electrophysiology in BLA coronal slices from four inbred mouse strains (A/J, BALBcJ, C57BL/6J and DBA2/J) to examine how genetic background influences acute ethanol effects on synaptic vesicle recycling and post-tetanic potentiation in response to low (2 Hz) and high (40 Hz) frequency stimulation.
Results
We found that ethanol inhibited synaptic vesicle recycling in a strain- and stimulation frequency-dependent manner. Vesicle recycling in DBA/2J and BALBcJ cells was inhibited by acute ethanol during both low and high frequency stimulation while recycling measured from AJ cells was sensitive only during high frequency stimulation. Recycling at C57BL/6J synapses was insensitive to ethanol regardless of stimulation frequency. We additionally found that cells from DBA/2J and BALBcJ mice were sensitive to ethanol-mediated inhibition of post-tetanic potentiation.
Conclusions
Acute ethanol application inhibited vesicle recycling and post-tetanic potentiation at glutamatergic synapses in both a strain- and frequency-dependent fashion. Several presynaptic proteins that contribute to synaptic vesicle priming in addition to post-tetanic potentiation have been implicated in alcohol-related behaviors, including Munc13, Munc18, and RIM proteins, making them potential candidates for the molecular mechanism controlling these effects.