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

Abstract

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.

Keywords: aversive; devaluation; discrimination; motivation; salience; value.

Figure 1.

A, The experimental design for simple and absolute inflation. B, C, Freezing is presented in terms of the percentage of time for pavlovian threat conditioning (PTC; B) and the test session (C). *Significance at α = 0.05.

Figure 2.

A, The experimental design for habituation with the klaxon outcome. B, C, Freezing is again presented in terms of the percentage of time for the pavlovian conditioning phase (B) and the subsequent test session (C). D, Freezing from a follow-up test where conditioned freezing to a shock-paired white noise was measured to determine whether klaxon habituation produced a hearing deficit. *Significance at the 0.05 α level. Hab, Habituation; PTC, pavlovian threat conditioning; Ctx, context-exposed control.

Figure 3.

A, Test data from the within-subject animal discrimination experiment. These data are displayed in terms of the percentage of time freezing to each CS as a function of the signaled outcome for the context-exposed controls (Ctx) as well as the inflated (Inf) and habituated (Hab) experimental groups. B, Test data from BA KORD-expressing subject animals that had undergone inflation and were treated with either Sal-B or the vehicle before the discrimination test session. C, Test data for BA KORD-expressing subject animals that had undergone inflation in a simple nondiscrimination design and were treated with either Sal-B or vehicle before the single-CS test session. D, Test data from controls treated with Sal-B but without KORD expression. E, The progression of experimental phases for studying changes to absolute and relative threat. *Significant effects at α = 0.05.

Figure 4.

A, Responses of cells during a baseline period and following Sal-B treatment. B, The minimum (red) and maximum (blue) extent of viral expression for subject animals treated with KORDs at the 1.56, 2.04, 2.64, and 3.24 mm posterior to bregma (images adapted from Paxinos and Watson, 2013). C, An image of a coronal section being tested for responses. D, The location of stimulating and recording electrodes can be seen in this image as well as the in schematic. E, A representative coronal section expressing KORD in BA using very intense purple (VIP).