Fig. 4: Alcohol binge drinking disinhibits pyramidal neurons and increases pyramidal intrinsic excitability, while chemogenetic silencing of pyramidal neurons reduces alcohol consumption.

A Representative sIPSC traces in PL L2/3 pyramidal neurons in control and binge drinking mice in both sexes. B Binge drinking reduced sIPSC frequency in pyramidal neurons. C Binge drinking did not alter sIPSC amplitude in pyramidal neurons. D No alterations in mIPSC frequency in pyramidal neurons. E No alterations in mIPSC amplitude in pyramidal neurons. F Representative traces of action potentials per current step in pyramidal neurons in control and binge drinking mice in both sexes. G Binge drinking did not alter RMP in either sex. H Binge drinking did not alter action potential threshold in either sex. I Pyramidal neurons in both sexes had lower rheobase following binge drinking. J Male pyramidal neurons produced more action potentials with increasing current injection amplitude following binge drinking. K Female pyramidal neurons produced more action potentials with increasing current injection amplitude following binge drinking. L Representative images of the hM4D(Gi) viral expression in PL pyramidal neurons. Scale bar 1 mm. (Right) Schematic of the experimental design. Both male and female C57BL/6 J mice were used in this experiment. M CNO-induced inhibition of PL pyramidal neurons decreased binge drinking in hM4D(Gi)-expressing mice. N Inhibition of PL pyramidal neurons was equally effective in reducing binge drinking in both male and female mice. *p < 0.05. **p < 0.01. Bonferroni’s post-hoc test.