, 2010). Notably, mPFC subregions have distinct functional implications for the HPA axis. While PLC dampens ACTH and corticosterone response selectively after restraint stress, IC does so only after a neuroimmunological type of stressor, but not after restraint stress (Radley et al., 2006). This reflects a distinct link between ventral and dorsal mPFC selleck chemical and the HPA axis. An important feature of the

ventral mPFC is its suggested role in the acquisition of stress resilience. Experience-driven resilience is a complex cognitive process involving progressive learning of a coping response. In animals, it can be modeled by exposure to a controllable stressor (tail shock) that can be actively terminated by the animal through running in a wheel, followed by exposure to another but uncontrollable shock in a novel context. The first shock progressively attenuates the escape response induced

by the second shock, resulting in “stress immunization.” Acquired resilience is long-lasting, protein synthesis-dependent and is mediated by glutamatergic pyramidal cells in ventral mPFC, which act as controllability detectors. These cells project onto GABAergic DRN interneurons and inhibit 5-HT neurons during controllable stress (Amat et al., 2006). During uncontrollable stress, memory of prior controllable experience elicits analogous DRN inhibition and mimics control. Stress resilience can also be acquired by prior exposure to an enriched environment but involves the IC in this case (Lehmann and Herkenham, 2011) and possibly its projections Selleck ZVADFMK to the hypothalamus, DRN, or amygdala. These projections are distinct from those emerging from PLC and ACC (Vertes, 2004). Finally, some of mPFC-mediated resilience can also result from suppression

of activity in the amygdala through reciprocal functional connections (Myers-Schulz and Koenigs, 2012). In addition to neural circuits in mPFC, circuits classically linked to reward also contribute to stress resilience. Behaviorally, the primary function of reward pathways is to favor goal-directed and motivated behaviors, decisions, positive actions and emotions, and optimism, which are all important mafosfamide traits of resilience. When these pathways are dysfunctional, motivation and drive are affected and mark the appearance of negative behaviors leading to depression (Pizzagalli et al., 2009). The reward circuitry is composed of the mesolimbic dopamine (DA) system, which includes DA neurons in the ventral tegmental area (VTA) projecting to NAc. While some DA neurons in NAc are inactive, others are spontaneously active and release DA differently depending on their firing pattern (Grace and Bunney, 1983). When firing with an irregular, low-frequency, single spike “tonic” pattern, DA release is tonic, while when firing with a bursting “phasic” pattern, DA is released in large phasic and transient peaks.