General and Specific Aversive Modulation of Active Avoidance Require Central Amygdala.

Three studies provide evidence that the central nucleus of the amygdala, a structure with a well-established role in conditioned freezing, is also required for conditioned facilitation of instrumental avoidance in rats. First, the immediate early gene c-Fos was measured following the presentation of a previously shock-paired tone in subjects trained either on an unsignaled avoidance task or not (in addition to tone only presentations in naïve controls). Significantly elevated expression of c-Fos was found in both the avoidance trained and Pavlovian trained conditions relative to naïve controls (but with no difference between the two trained conditions). In a subsequent study, intracranial infusions of muscimol into the central amygdala significantly attenuated the facilitation of shock-avoidance by a shock-paired Pavlovian cue relative to pre-operative responding. The final study used a virogenetic approach to inhibit the central amygdala prior to testing. This treatment eliminated the transfer of motivational control over shock-avoidance by both a shock-paired Pavlovian stimulus, as well as a cue paired with a perceptually distinct aversive event (i.e., klaxon). These findings provide compelling support for a role of central amygdala in producing aversive Pavlovian-instrumental transfer.

Motivational factors underlying aversive Pavlovian-instrumental transfer.

While interest in active avoidance has recently been resurgent, many concerns relating to the nature of this form of learning remain unresolved. By separating stimulus and response acquisition, aversive Pavlovian-instrumental transfer can be used to measure the effect of avoidance learning on threat processing with more control than typical avoidance procedures. However, the motivational substrates that contribute to the aversive transfer effect have not been thoroughly examined. In three studies using rodents, the impact of a variety of aversive signals on shock-avoidance responding (i.e., two-way shuttling) was evaluated. Fox urine, as well as a tone paired with the delivery of the predator odor were insufficient modulatory stimuli for the avoidance response. Similarly, a signal for the absence of food did not generate appropriate aversive motivation to enhance shuttling. Only conditioned Pavlovian stimuli that had been paired with unconditioned threats were capable of augmenting shock-avoidance responding. This was true whether the signaled outcome was the same (e.g., shock) or different (e.g., klaxon) from the avoidance outcome (i.e., shock). These findings help to characterize the aversive transfer effect and provide a more thorough analysis of its generalization to warning signals for different kinds of threats. This feature of aversive motivation has not been demonstrated using conventional avoidance procedures and could be potentially useful for applying avoidance in treatment settings.

Chemogenetic Inhibition Reveals That Processing Relative But Not Absolute Threat Requires Basal Amygdala.

While our understanding of appetitive motivation has benefited immensely from the use of selective outcome devaluation tools, the same cannot be said about aversive motivation. Findings from appetitive conditioning studies have shown that basal amygdala is required for behaviors that are sensitive to updates in outcome value, but similar results in aversive motivation are difficult to interpret due to a lack of outcome specificity. The studies reported here sought to develop procedures to isolate sensory-specific processes in aversive learning and behavior and to assess the possible contribution of the basal amygdala. Post-training changes to outcome value produced commensurate changes to subsequently tested conditioned responding in male rodents. Specifically, increases in shock intensity (i.e., inflation) augmented, while repeated exposure to (i.e., habituation of) an aversive sound (klaxon-horn) reduced freezing to conditioned stimuli previously paired with these outcomes. This was extended to a discriminative procedure, in which following revaluation of one event, but not the other, responding was found to be dependent on outcome value signaled by each cue. Chemogenetic inactivation of basal amygdala impaired this discrimination between stimuli signaling differently valued outcomes, but did not affect the revaluation process itself. These findings demonstrate a contribution of the basal amygdala to aversive outcome-dependent motivational processes.SIGNIFICANCE STATEMENT The specific content of pavlovian associative learning has been well studied in appetitive motivation, where the value of different foods can be easily manipulated. This has facilitated our understanding of the neural circuits that generate different forms of motivation (i.e., sensory specific vs general). Studies of aversive learning have not produced the same degree of understanding with regard to sensory specificity due to a lack of tools for evaluating sensory-specific processes. Here we use a variant of outcome devaluation procedures with aversive stimuli to study the role of basal amygdala in discriminating between aversive stimuli conveying different degrees of threat. These findings have implications for how we study generalized threat to identify dysregulation that can contribute to generalized anxiety.

Pavlovian Extinction and Recovery Effects in Aversive Pavlovian to Instrumental Transfer.

Three studies explored the sensitivity of aversive Pavlovian to instrumental transfer (PIT) to Pavlovian extinction in rodents. Rats underwent Pavlovian conditioning prior to avoidance training. The PIT test then involved assessment of the effects of the Pavlovian conditioned stimulus (CS) on the performance of the avoidance response (AR). Conducting extinction prior to avoidance training and transfer testing, allowed spontaneous recovery and shock reinstatement of extinguished motivation, whereas conducting extinction following avoidance training and just prior to PIT testing successfully reduced transfer effects. This was also the case in a design that compared responding to an extinguished CS against a non-extinguished CS rather than comparing extinguished and non-extinguished groups to one another. While extinction treatments in many appetitive PIT studies do not successfully reduce transfer, and can sometimes enhance the effect, the current findings show that an extinction treatment temporally close to transfer testing can reduce the motivational impact of the aversive Pavlovian CS on instrumental avoidance responding.