Neuroplasticity mechanisms of resilience

Our data above from a weaker version of LH (wLH, Fig. 2d), which maximizes individual variability in escape behavior, suggest that DA-dependent plasticity correlates with behavioral outcome after aversive learning. Animals that escape more after wLH have a higher probability of glutamate-evoked spinogenesis. The relationship is somewhat weakened after ketamine (smaller slope and R2), yet it persists. DA-dependent plasticity in mPFC therefore correlates with individual resilience. Ketamine, similar to other anti-depressants, has shown variable efficacy across patients, and our data suggest that tailoring treatment based on individual differences in DA-dependent plasticity may be a promising route for improving efficacy. Here, we seek to further understand neural activity and plasticity signatures associated with resilience and to enhance it, via the following two aims: Aim I. Evaluate enhancers of spinogenesis in mPFC as markers of resilience in aversive learning Aim II. Determine neural activity mechanisms of individual resilience in DA signaling