Fig. 2: Chronic Ethanol Exposure impairs LTPGABA in a Presynaptic manner in VTA DA Neurons. | Molecular Psychiatry

Fig. 2: Chronic Ethanol Exposure impairs LTPGABA in a Presynaptic manner in VTA DA Neurons.

From: BDNF restores impaired long-term potentiation of GABAergic synapses induced by chronic ethanol exposure in the VTA and attenuates reward-seeking behavior

Fig. 2: Chronic Ethanol Exposure impairs LTPGABA in a Presynaptic manner in VTA DA Neurons.

(A) Schematic of the recording configuration in a VTA slice. The red dot indicates a recorded DA neuron, and the bipolar stimulating electrode (stim) was placed rostral to the VTA. MT, medial terminal nucleus of the accessory optic tract. (B) Representative images of the recording. Top: A VTA slice under a 10x objective. Bottom: A patched DA neuron (indicated by the pipette) under a 40x objective. (C) Identification of a putative DA neuron by a large hyperpolarization-activated current (Ih). A voltage at -110 mV elicited an Ih >100 pA. (D) Pharmacological isolation of GABAA receptor-mediated eIPSC. Bath application of 100 µM picrotoxin (PTX) blocked the evoked currents. (E) High-frequency stimulation (HFS, 100 Hz) induced LTPGABA in slices from ethanol-naïve (water control) mice. Insets show average eIPSC traces before (black) and 20-25 min after HFS (red). (F) HFS failed to induce LTPGABA in slices from chronic ethanol-exposed mice. (G) Time course of normalized eIPSC amplitude before and after HFS for control (black, n = 8 cells/6 mice) and chronic ethanol exposed group (red, n = 6 cells/6 mice). Data are mean ± SEM. (H) Summary of mean eIPSC amplitude before and after HFS in control mice (Before: 183.8 ± 24.01 pA; After: 331.7 ± 48.96 pA; paired t-test, p < 0.01). (I) Summary of mean eIPSC amplitude before and after HFS in chronic ethanol-exposed mice (Before: 331.8 ± 56.45 pA; After: 338.3 ± 53.25 pA; paired t-test, p > 0.05). (J) Time course of normalized paired-pulse ratio (PPR) before and after HFS (black for water group, n = 8 cells/6 mice; red for chronic ethanol exposed group, n = 6 cells/6 mice). (K) Summary of PPR before and after HFS in control mice (Before: 0.96 ± 0.05; After: 0.80 ± 0.03; paired t-test, p < 0.05). (L) Summary of PPR before and after HFS in chronic ethanol-exposed mice (Before: 0.79 ± 0.03; After: 0.75 ± 0.05; paired t-test, p > 0.05). (M) Time course of normalized 1/CV2 before and after HFS (black for water group, n = 8 cells/6 mice; red for chronic ethanol exposed group, n = 6 cells/6 mice). (N) Summary of 1/CV2 before and after HFS in control mice (Before: 13.02 ± 1.88; After: 28.17 ± 6.08; paired t-test, p < 0.05). (O) Summary of 1/CV2 before and after HFS in chronic ethanol-exposed mice (Before: 50.18 ± 34.11; After: 69.08 ± 41.85; paired t-test, p > 0.05). All summary bar graphs show mean ± SEM. *p < 0.05, **p < 0.01, n.s., not significant.

Back to article page