The ethanol inhibition of basolateral amygdala neuron spiking is mediated by a γ‐aminobutyric acid type A‐mediated tonic current

• Published in: Alcoholism, clinical and experimental research clinical and experimental research, 2022-09, Vol.46 (9), p.1665-1676
• Main Authors: Nimitvilai‐Roberts, Sudarat, Woodward, John J.
• Format: Article
• Language: English
• Subjects: Action potential; Alcohol use; Alcoholism; Amygdala; Animals; Anxiety; basolateral amygdala; Basolateral Nuclear Complex; Brain slice preparation; Caudate-putamen; Central Amygdaloid Nucleus; Cortex (frontal); Cortex (somatosensory); Drug abuse; Drug dependence; Ethanol; Ethanol - pharmacology; Excitability; Firing pattern; GABAA‐mediated tonic currents; gamma-Aminobutyric Acid - pharmacology; Glycine receptors; Information processing; Inhibitory postsynaptic potentials; intrinsic excitability; Male; Membrane potential; Mice; Mice, Inbred C57BL; Neostriatum; Neurons; Picrotoxin; Picrotoxin - pharmacology; Receptors, GABA-A - physiology; Receptors, Glycine; Sensory integration; Sensory stimuli; Strychnine; Strychnine - pharmacology; Synaptic Transmission; γ-Aminobutyric acid A receptors
• ISSN: 0145-6008; 1530-0277
• DOI: 10.1111/acer.14918

Background The basolateral nucleus of the amygdala (BLA) plays an important role in the development of fear and anxiety‐related behaviors. The BLA receives inputs from all sensory stimuli. After processing those stimuli, BLA neurons signal neurons within the central amygdala and other brain regions, including the ventral and dorsal striatum and frontal cortex. Studies suggest that the BLA is involved in drug dependence and in the reinforcing actions of ethanol. For example, acute exposure to ethanol reduces anxiety, while withdrawal from chronic ethanol exposure alters BLA synaptic transmission, which increases anxiety, a common underlying cause of relapse. Exposure to and withdrawal from chronic alcohol also disrupts many brain areas that connect with the BLA. Despite these important findings, the acute actions of alcohol on the intrinsic excitability of BLA neurons have not been fully characterized. Methods Brain slices containing the BLA were prepared from adult C57BL/6J male mice. Whole‐cell and sharp electrode electrophysiological recordings were performed to characterize the effects of acute ethanol on BLA neuronal and astrocyte function, respectively. Results Ethanol inhibited action potential (AP) firing of BLA neurons but had no effect on BLA astrocyte resting membrane potential. The ethanol‐induced inhibition of firing was concentration‐dependent (11 to 66 mM) and accompanied by a reduction in the input resistance and an increase in the rheobase of BLA neurons. The inhibitory effect of ethanol was suppressed by picrotoxin, which blocks both γ‐aminobutyric acid type A (GABAA) and glycine receptors, but not by the selective glycine receptor antagonist strychnine, which suggests an involvement of GABAA receptors. Ethanol did not affect spontaneous inhibitory postsynaptic currents suggesting that the inhibition of BLA neuronal excitability by ethanol was not due to an increase in GABAA‐mediated synaptic transmission. However, acute ethanol enhanced the amplitude of the holding current of BLA neurons, an effect that was prevented by picrotoxin, which by itself reduced the holding current. Conclusions These results suggest that BLA neurons express a GABA‐mediated tonic current that is enhanced by acute ethanol, which leads to reduced excitability of BLA neurons. The basolateral amygdala (BLA) is a key regulator of reward including that associated with ethanol drinking. We used slice electrophysiology and showed that acute ethanol inhibited BLA neuron s