Article Figures & Data
Figures
- Figure 1.
Chronic social defeat stress increases the firing rates and bursting events in VTA DA neurons in susceptible, not resilient (unsusceptible), mice. A , Timeline of chronic social defeat, behavioral testing, and in vivo recording protocols. B , The time spent in the interaction zone during a social interaction test (***p < 0.0001 vs control or unsusceptible; 8–20 mice/group). C , Sample traces, bursting events, and spikes for in vivo recordings from VTA DA neurons from control, susceptible, and unsusceptible mice. D , Overall VTA firing rates in control, susceptible, and unsusceptible mice (***p < 0.0001 vs control or unsusceptible mice, n = 58–72 cells, 15 mice/group). E , Average VTA firing rate for each mouse is significantly negatively correlated with the time spent in interaction zone measured on day 11 (p < 0.05, n = 35 mice). F , H , J , Burst-firing events of VTA DA neurons, including percentage of burst-firing cells, percentage of spikes in bursts, and number of spikes in a burst, were increased in susceptible, not unsusceptible, mice (**p < 0.01, ***p < 0.001 vs control or unsusceptible mice; n = 23–49 cells, 8–15 mice/group). G , I , K , The average changes of these bursting events for each animal also inversely correlated with its social interaction time (p < 0.05; n = 35 mice). L , Scatter plot of the bursting activity and firing rates of all neurons recorded from control, susceptible, and unsusceptible mice. Note the large number of VTA DA neurons in susceptible mice with high firing rate and more bursting activity. Firing rates are significantly positively correlated with percentage of spikes in bursts in all three groups, suggesting the increased firing rates were associated with the increase of bursting events (control: r 2 = 0.127, n = 65 cells/15 mice, p < 0.001; susceptible: r 2 = 0.0952, n = 72 cells/12 mice, p < 0.001; unsusceptible: r 2 = 0.0758, n = 58 cells/8 mice, p < 0.05).
- Figure 2.
Chronic treatment with fluoxetine normalizes stress-induced maladaptations of VTA DA neurons in susceptible mice. A , Timeline of chronic social defeat, behavioral testing, treatment with fluoxetine, and in vivo recording protocols. B , Chronic, not acute, administration of fluoxetine normalized defeat-induced avoidance behavior in susceptible mice (**p < 0.01 vs susceptible-vehicle mice, 5–7 mice/group). C , Sample traces for in vivo recordings from VTA DA neurons from susceptible mice with acute or chronic treatment with vehicle or fluoxetine. D , Cumulative probability distribution plots of VTA firing rates in susceptible mice after acute or chronic treatment with vehicle or fluoxetine. E , Acute or chronic treatment with vehicle or fluoxetine did not change the firing rates of VTA DA neurons in control mice (p > 0.5, n = 46–48 cells, 5 mice/group), and chronic, not acute, administration of fluoxetine normalized the increased firing rates of VTA DA neurons in susceptible mice (***p < 0.001 vs susceptible-vehicle or susceptible-acute mice; n = 43–64 cells, 5–6 mice/group). F–H , Acute or chronic treatment with vehicle or fluoxetine did not change burst events of VTA DA neurons in control mice (p > 0.5, n = 20–21 cells, 5 mice/group), however, chronic, not acute, administration of fluoxetine reversed the increased burst events of VTA DA neurons in susceptible mice (*p < 0.05, **p < 0.01 vs susceptible-vehicle or susceptible-acute mice, n = 22–45 cells, 5–6 mice/group). I , Scatter plot of percentage of spikes in bursts and firing rates of all neurons recorded from susceptible-vehicle (n = 61), susceptible-acute (n = 50), and susceptible-chronic (n = 43) mice. Note the small number of VTA DA neurons with high firing rates and more bursting activity in susceptible mice after chronic treatment with fluoxetine.
- Figure 3.
Ih channels in VTA DA neurons were involved in defeat-induced avoidance behavior and action of fluoxetine. A , Ih currents were elicited by repetitive 800 ms pulses with 10 mV increments from a holding potential of −60 to −140 mV. Sample traces recorded from control-vehicle, susceptible-vehicle, and susceptible-fluoxetine mice. B , Chronic social defeat increased Ih currents in VTA DA neurons, which was almost completely reversed by chronic treatment with fluoxetine (***p < 0.0001 vs control-vehicle mice, ## p < 0.01 vs susceptible-fluoxetine mice, n = 35–66 cells, 10–12 mice/group). C , Infusion of Ih channel inhibitor ZD7288 or DK-AH 269 into VTA significantly reversed the stress-induced social avoidance (**p < 0.01, ***p < 0.001; n = 6–11 mice).
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