Acute ethanol inhibits asynchronous glutamate release from mouse basolateral amygdala synapses

Area of Science:

• Neuroscience
• Neuropharmacology
• Synaptic Plasticity

Background:

• Acute ethanol affects numerous neurotransmitter systems, but its presynaptic regulation of glutamatergic function is not well understood.
• Previous studies suggest ethanol inhibits glutamatergic responses from recycling vesicles in the basolateral amygdala (BLA).

Purpose of the Study:

• To investigate the hypothesis that acute ethanol modulates actively priming synaptic vesicles in glutamate synapses.
• To examine the effects of acute ethanol on asynchronous synaptic transmission in BLA principal neurons.

Main Methods:

• Whole-cell patch-clamp recordings were performed in BLA principal neurons.
• Asynchronous synaptic transmission was measured under conditions of increased presynaptic activation and elevated presynaptic calcium.
• The effects of varying ethanol concentrations and the calcium chelator EGTA were assessed.
• Experiments were conducted using DBA/2J and C57BL/6J mouse strains.

Main Results:

• Acute ethanol inhibited EGTA-sensitive asynchronous glutamatergic responses in a concentration-dependent manner.
• Ethanol's inhibitory effect was observed under conditions of increased presynaptic activation and elevated calcium.
• This modulation was present in DBA/2J mice but absent in C57BL/6J mice.
• EGTA, which suppresses asynchronous release, occluded ethanol's modulation of asynchronous events but not recycling vesicle responses.

Conclusions:

• Acute ethanol uniquely affects asynchronous glutamate vesicle priming pathways.
• Ethanol's action on asynchronous release is dependent on specific presynaptic mechanisms and mouse strain.
• These findings reveal a novel mechanism of ethanol's influence on glutamatergic neurotransmission.