To this point, recent work by Luthi and colleagues has shown that there are anatomically distinct populations of neurons in the basolateral amygdaloid nucleus that respond when animals express either express or suppress conditional fear (Herry et al., 2008). “Fear” neurons responded to nonextinguished CSs or extinguished CSs presented outside the extinction context, whereas extinction

neurons only responded to extinguished CSs presented in their extinction context. Interestingly, the majority of fear neurons were orthodromically activated by electrical stimulation of the ventral hippocampus, whereas extinction neurons received their afferent input from the vmPFC. Hence, the contextual retrieval of fear memory might involve VX-809 datasheet a hippocampo-prefrontal

cortical network that regulates the balance of excitation and inhibition in the amygdala to foster or suppress, respectively, fear to an extinguished CS (Maren, 2005). It is also conceivable that the balance of activity among inhibitory CEl neurons that are either excited (“CS on” neurons) or inhibited (“CS off” neurons) by a CS (e.g., Ciocchi et al., 2010) regulates the suppression or renewal, respectively, of fear after extinction; find more this possibility has not yet been explored. Reducing the expression of fear memory with extinction procedures, such as exposure therapy, is fundamental to therapeutic interventions for fear and anxiety disorders in humans. Unfortunately, the suppression of conditional responding that follows extinction is transient (Bouton, 1993, Bouton and Bolles, 1979a and Rescorla, 2004). In his early work, Pavlov noted that an extinguished CR would return if the animal was presented with a novel stimulus, a phenomenon termed “disinhibition” (Pavlov, 1927). He also showed that extinguished CRs would spontaneously return with the mere passage of time, a phenomenon termed “spontaneous

recovery.” As previously described, extinguished CRs are also highly specific to the experimental context in which they are acquired. In other words, an extinguished CR exhibits “renewal” when the CS is presented outside the extinction context. Similarly, unsignaled USs can restore extinguished responding when the CS is presented in the context in which the US was delivered. This phenomenon is whatever termed “reinstatement” (Bouton and Bolles, 1979b and Rescorla and Heth, 1975). These phenomena indicate that extinction does not erase the conditioning memory, rather it causes new learning about the CS. Indeed, it appears that extinction training yields a new “safety” memory that inhibits retrieval of the fear memory. Unlike fear memory, the expression of this safety memory is limited by context and time (Bouton, 1993). “Context” is defined broadly to include the experimental environment and interoceptive state of the animal, as well as the actual (time of day) and relative time (how long ago) the events were learned.