Article Figures & Data
Figures
- Figure 1.
Behavioral results during exposure to escapable shock and inescapable shock. A, A schematic of conditioning operant chamber. Mice terminated footshock after nose poking through the active, but not inactive, nosepoker. B, Procedures of escapable shock and inescapable shock in the LOC group. C, The number of active and inactive nose pokes during acclimation for 100 min (NS: n = 41, L-Yoked: n = 30, LOC: n = 30, ES: n = 18). D, Average escape latencies from day 1 to day 6 in the LOC and ES groups (LOC: n = 30, ES: n = 18). LOC and L-Yoked groups received the identical shock. E, The number of active and inactive nose pokes from day 1 to day 6 in the LOC, L-Yoked, and ES groups (LOC: n = 30, L-Yoked: n = 30, ES: n = 18); ***p < 0.001. Error bars represent SEM. NS: no shock; ES: escapable shock; LOC: loss of control over shock; L-Yoked: yoked to LOC.
- Figure 2.
Both lack and loss of control over shock increase the activity of SNc DA neurons. A, Timeline of LOC model, shuttle box test, and in vivo recordings. B, Representative in vivo SNc DA neuron firing traces for the NS, ES, L-Yoked, and LOC mice. C, Mean escape latencies of 25 FR2 escape trials in the shuttle box test on day 7 (n = 7 per group). D, SNc DA neuron firing rates in the LOC, L-Yoked, ES, and NS mice. E, SNc DA neuron percentage of bursting firing cells among the four groups. F, SNc DA neuron frequency of busting among the four groups. G, SNc DA neuron percentage of spikes in bursts among the four groups. H, Correlation between average SNc DA neuron firing rates and mean escape latencies in the shuttle box test in all four groups (n = 28 mice). I, Correlation between average SNc DA neuron frequency of bursting and mean escape latencies in the shuttle box test in all four groups (n = 28 mice). J, Correlation between average SNc DA neuron percentage of spikes in bursts and mean escape latencies in the shuttle box test in all four groups (n = 28 mice); *p < 0.05, **p < 0.01, ***p < 0.001. Error bars represent SEM. NS: no shock; ES: escapable shock; LOC: loss of control over shock; L-Yoked: yoked to LOC. NS: n = 53 cells from 7 mice; ES: n = 46 cells from 7 mice; L-Yoked: n = 49 cells from 7 mice; LOC: n = 38 cells from 7 mice.
- Figure 3.
Dynamic changes in the level of serum corticosterone following the stress exposure. A, Timeline of stress exposure, shuttle box test, and taking blood to determine serum corticosterone concentrations. B, The levels of serum corticosterone 2 min after stress exposure at various time (days 1, 4, 6, and 7 after the shuttle box test). LOC mice were exposed to escapable shocks on days 1–3, and then to inescapable shocks on days 4–6, with L-Yoked mice receiving the identical inescapable shocks. ES mice were exposed to escapable shocks on days 1–6. NS mice were placed in the same environment but receiving no shock. On day 7, the four groups were exposed to shuttle box test. C, Mean escape latencies of 25 FR2 escape trials in shuttle box test; *p < 0.05, **p < 0.01, ***p < 0.001. Error bars represent SEM. CORT: corticosterone. LOC: loss of control over shock; L-Yoked: yoked to LOC; ES: escapable shock; NS: no shock. n = 5 per group.
- Figure 4.
Both lack and loss of control over shock increase the excitability of SNc DA neurons. A, Timeline of LOC model and in vitro recordings. B, Input membrane resistance (Rinput) of SNc DA neurons. C, Membrane capacitance (Cm) of SNc DA neurons. D, Representative Ih traces (left) and I-V graph of Ih (right). E, Representative spike traces after current injection (left, 200 pA) and the number of spikes elicited to current injections of SNc DA neurons from the LOC, L-Yoked, and NS mice; *p < 0.05, **p < 0.01, ***p < 0.001 versus LOC group; #p < 0.05, ##p < 0.01 versus L-Yoked group. Error bars represent SEM. NS: no shock; ES: escapable shock; LOC: loss of control over shock; L-Yoked: yoked to LOC. NS: n = 55 cells from 6 mice; ES: n = 58 cells from 6 mice; L-Yoked: n = 65 cells from 6 mice; LOC: n = 51 from 6 mice.
- Figure 5.
Loss of control over shock decreases the natural reward-induced calcium signal of SNc DA neurons. A, Timeline of LOC model and fiber photometry. B, Fiber photometry of calcium signal from freely behaving mice voluntarily licking sucrose solution. C, Expression of GCaMP6m (green) in TH-immunopositive neurons (red) in the SNc of a DAT-Cre mouse. D, Raw traces from expressing GCaMP6m (top) and eYFP (bottom) in the SNc of the DAT-Cre mice during the sucrose solution intake. GCaMP6m fluorescence showed a robust increase during the sucrose licking epochs (res dashes). E, Peri-event plots of average calcium signals during licking sucrose solution before and after stress exposure in the NS, ES, L-Yoked, and LOC groups, respectively. Red color superimposed on the black solid and dashed line indicate significant increases from baseline (p < 0.001). F, Quantification of SNc fluorescence evoked by licking sucrose solution before and after stress exposure in the NS, L-Yoked, LOC, and ES groups (**p < 0.01). AUC, area under curve. Error bars represent SEM. NS: no shock; LOC: loss of control over shock; L-Yoked: yoked to LOC; ES: escapable shock. NS: n = 8, L-Yoked: n = 7, LOC: n = 7, ES: n = 7.
Extended Data
Extended Data Figure 1-1
LOC over shock produced significant depression-like behaviors. A, In the SPT, the LOC group exhibited a significant reduction in sucrose preference index, as compared with the other three groups. Preference index is calculated as the ratio of the number of licks for the sucrose solution to the total number of licks. B, In the FST, both the LOC and the L-Yoked groups exhibited significantly longer immobile time than the ES and the NS groups, respectively. In addition, the LOC group showed even longer immobile time than the L-Yoked group; *p < 0.05, **p < 0.01, ***p < 0.001. Error bars represent SEM. LOC: loss of control over shock; L-Yoked: yoked to LOC; ES: escape shock; NS: no shock. NS: n = 8, L-Yoked: n = 8, LOC: n = 8, ES: n = 6. Download Figure 1-1, TIF file.
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