Fig. 4: Social stress shifts the balance of excitation and inhibition more towards excitation at LHA control over the VTA dopamine system. | Nature Communications

Fig. 4: Social stress shifts the balance of excitation and inhibition more towards excitation at LHA control over the VTA dopamine system.

From: Stress-driven potentiation of lateral hypothalamic synapses onto ventral tegmental area dopamine neurons causes increased consumption of palatable food

Fig. 4

a Timeline and schematic for stress protocol for electrophysiological patch clamp experiments of VTADA and VTAGABA neurons. b GABAAR-AMPAR ratios at LHA-VTADA synapses decreased post stress. Left: representative AMPAR and GABAAR traces. Blue rectangle: start of LED stimulation. Scale bar: 25 pA, 20 ms. Right: Cumulative probability plot quantification (n cells control = 23, n cells stress = 25, KS-test, D = 0.499, p = 0.003). c GABAAR-AMPAR ratio at LHA-VTAGABA synapses. Left: representative AMPAR and GABAAR traces. Scale bar: 40 pA, 25 ms. Right: Cumulative probability plot quantification (n cells control = 25, n cells stress = 29, KS-test, D = 0.34, p = 0.074). d Left: Schematic of patch clamp experiments of VTADA neurons projecting to mPFC. Right: representative image of viral expression of retroAAV-DIO-mCherry (+ diluted red beads for injection site verification) in horizontal sections. mPFC (top) Scale bar: 100 µm, VTA (bottom) scale bar: 20 µm. Anatomical reference points cc corpus callosum, CPu caudate putamen. e AMPAR Rectification index increases at LHAglu-VTADA-mPFC synapses after stress. Left: example traces, scale bars: 50 ms, 25 pA. Middle: AMPAR current at −60 mV, 0 mV and +40 mV normalized to AMPAR current at −60 mV (n cells control = 7, n cells stress = 9). Right: Averages + SEMs (n cells control = 7, n cells stress = 9, KS-test, D(1,15) = 1.70, p = 0.006). f Timeline and schematic for in vivo fiber photometry experiment to assess mPFC dopamine release as a function of LHAglu-VTA stimulation. g Representative images of CochR-GFP virus expression in LHAglu cells (green), optogenetic stimulation fiber above the VTA, dLight expression in the PFC (green) with a photometry fiber. Scale bars: 100 µm. Anatomical reference points: f fornix, EPN entopeduncular nucleus, mt mammillo-thalamic tract. h Left: Average +SEM of emitted fluorescence in mPFC for LHAglu-VTA stimulation frequencies of 20, 33 and 50 Hz for pre and post stress (n mice = 6). Right: Averages + SEMs. Stress increases dopamine release in mPFC post-stress, peak DA release (RM Two-Way ANOVA. Main effect stress F(1,5) = 6.92, p = 0.047). Scale bars: 10 s, 0.05 dF/F. All statistical tests were performed two-sided. *p < 0.05, **p < 0.01. Source data are provided as a Source Data file.

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