Stress is a pivotal factor in the neurobiology of depression, a condition that shares high rates of co-morbidity with addiction, and a persistent or an aberrant synaptic plasticity state within DA neurons can affect an individuals susceptibility or resilience to stress throughout life. This is why our findings may be relevant toward the understanding of post-traumatic stress disorder (PTSD) pathophysiology. In fact, several clinical studies have investigated and emphasized that PTSD arises from aberrant emotional learning mechanisms. Traumatic experiences can be seen as an unconditioned stimulus and recurrent clinical symptoms as a conditioned response. Psychiatric conditions, such as PTSD, are chronic, invalidating, and relapsing disorders that are potentially the result of the loss of fear response extinction Moreover, the chronic nature of the condition leads to an aberrant rumination of trauma-related cues that over time may affect, by virtue of second-order conditioning, emotional aspects of future meaningful experiences that come to acquire some of the fearful properties of the original traumatic event. Accordingly, our animal model displays a higher degree of behavioral responses when it comes to assigning motivational value to events that are intrinsically aversive or conditioned to be unpleasant. In summary, our results highlight a fundamental, novel role for synaptic plasticity within DAT+ neurons in shaping adaptive responses to negatively charged emotional experiences.
| Tejeda, Hugo A; Wu, Jocelyn; Kornspun, Alana R et al. (2017) Pathway- and Cell-Specific Kappa-Opioid Receptor Modulation of Excitation-Inhibition Balance Differentially Gates D1 and D2 Accumbens Neuron Activity. Neuron 93:147-163 |
