Figure 4. Extracellular levels of serotonin (5-HT) within the dorsal raphe nucleus (DRN), as a percentage of baseline, before, during, and after inescapable shock (IS). Separate groups received either escapable shock (ES), yoked inescapable (IS), or home cage control … Fear conditioning and the amygdala To this point we have focused Inhibitors,research,lifescience,medical on the interaction between the mPFCv and

the DRN, with control leading to protection against the effects of aversive events by increasing mPFCv inhibition of the DRN. However, the mPFCv projects to other stressresponsive structures as well. The amygdala is of special interest in this regard. The amygdala is a key site in the mediation of fear and anxiety Its role in fear conditioning is well known, and fear conditioning has been argued to be a key process in the development of a number of anxiety disorders.34 The work of numerous Inhibitors,research,lifescience,medical investigators has suggested the following scenario (see ref 35 for a review). Inputs from neutral stimuli (the conditioned stimulus [CS], eg, a tone) and aversive

stimulation Inhibitors,research,lifescience,medical (the unconditioned stimulus [US], eg, a footshock) converge in the lateral amygdala (LA) where the association between the CS and US is formed by an AmethylDaspartate (NMDA)/longterm potentiation (LTP)-dependent process. Expression of conditioned fear involves CS transmission to the LA, connections from the LA to the central nucleus of the amygdala (CE) either directly or indirectly via the basal nucleus, and then output connections Inhibitors,research,lifescience,medical from the CE to regions of the brain that are the proximate mediators of the specific aspects of fear responses (autonomic, endocrine, and behavioral). This is an oversimplified scheme (eg, 36, 37), but it nevertheless Everolimus captures a large amount of data. In the present context, it is interesting to note that the mPFCv projects Inhibitors,research,lifescience,medical to the amygdala,38 and stimulation of the mPFCv has been reported to inhibit the increase in electrical activity in

the LA produced by an already conditioned fear stimulus, as well as the fear response to that stimulus, and to prevent the association between CS and US when they are paired.39 Similarly, Quirk et al40 found that mPFCv stimulation reduces Sclareol output from the CE in response to electrical stimulation of input pathways to the CE, and Milad et al41 found mPFCv stimulation to reduce fear responses produced by a fear CS. Although the exact projections of the mPFCv to the amygdala responsible for the inhibition of fear conditioning and fear responses resulting from mPFCv stimulation are unclear, the mPFCv does project to the intercalated cell mass (ITM) within the amygdala. These cells are almost all GABAergic, and project to the CE, providing an obvious pathway by which mPFCv activation could inhibit the CE.