However, Warden et al. (Warden et al., 2012) have reported that selective optogenetic activation of the vmPFC-to-DRN pathway reduces inactivity in a swim test. Detecting/processing the presence of control and regulating the DRN as a consequence Z VAD FMK are conceptually separable functions. The research summarized above clearly indicates that the mPFC is involved in regulating the DRN under conditions in which a stressor is controllable via its descending projections, but does the mPFC by itself also detect that the stressor is controllable? A consideration of the concept of control suggests

an intriguing possibility. Maier and Seligman (Maier and Seligman, 1976) defined control over a stressor with selleck kinase inhibitor regard to the difference between 2 conditional probabilities—the conditional probability of the stressor being altered (e.g., shock termination) given that a behavioral response (e.g., turning the wheel) has occurred and the conditional probability of the stressor being altered given that the response has not occurred. Control is present whenever the 2 probabilities are unequal. Under this circumstance, the probability of stressor alteration can be increased either by making, or withholding a response. When the 2 probabilities are equal there is nothing that the organisms can do to alter the adverse event, that is, it is uncontrollable. Interestingly, research concerning the neural mechanisms

that mediate appetitive instrumental learning has involved a similar concept. There has been a long debate as to whether such learning involves the formation of a Stimulus-Response habit or instead a Response-Reinforcer expectancy. Work at the neural level has made it clear that both can take place and involve different neural systems (Balleine and O’Doherty,

2010). One system, called the act/outcome system, is said to be sensitive to the contingency between response and reinforcer. Contingency has been defines as “the difference between the probability of obtaining a target reward (r) given that a specific action (a) is performed and the probability of gaining the reward in the absence of the action” ((Liljeholm et al., 2011) p. 2474). The act/outcome system leads to “flexible” learning, and is sensitive to changes in the outcome or reward. A second next system, called the habit system, is not sensitive to contingency but instead to only the temporal pairing between response and reward, and produces inflexible learning not sensitive to changes in the characteristics of the reward (Balleine and Dickinson, 1998). A large body of work indicates that the act/outcome system involves a corticostriatal circuit consisting of the PL and the posterior dorsal medial striatum (DMS), while the habit system has no prefrontal cortical involvement, but instead sensorimotor cortex and the dorsal lateral striatum (DLS).