Input-specific contributions to valence processing in the amygdala

Abstract

Reward and punishment are often thought of as opposing processes: rewards and the environmental cues that predict them elicit approach and consummatory behaviors, while punishments drive aversion and avoidance behaviors. This framework suggests that there may be segregated brain circuits for these valenced behaviors. The basolateral amygdala (BLA) is one brain region that contributes to both types of motivated behavior. Individual neurons in the BLA can favor positive over negative valence, or vice versa, but these neurons are intermingled, showing no anatomical segregation. The amygdala receives inputs from many brain areas and current theories posit that encoding of positive versus negative valence by BLA neurons is determined by the wiring of each neuron. Specifically, many projections from other brain areas that respond to positive and negative valence stimuli and predictive cues project strongly to the BLA and likely contribute to valence processing within the BLA. Here we review three of these areas, the basal forebrain, the dorsal raphe nucleus and the ventral tegmental area, and discuss how these may promote encoding of positive and negative valence within the BLA.

Figure 1.

Proposed models representing how opposing valence behaviors are generated by basolateral amygdala neurons (BLA). (A) Model 1. Individual BLA neurons have anatomical segregation of both inputs and outputs, such that inputs that carry appetitive information synapse onto BLA neurons that project to brain regions that regulate approach behaviors, while inputs that carry aversive information synapse onto BLA neurons that regulate avoidance behaviors. (B) Model 2. Individual BLA neurons receive inputs conveying both rewarding and aversive reinforcers, but only control either appetitive or avoidance behaviors. (C) Model 3. Individual BLA neurons receive information about both rewarding and aversive reinforcement and project to brain regions that can control both approach and avoidance behaviors. According to this model, the role of BLA neurons in valence driven behaviors is dynamic and may be altered by experience.

Figure 2.

Proposed model representing how neurons in the nucleus basalis magnocellularis (NB) may convey valence information to BLA neurons. This model shows that NB neurons with segregated function may project to similar neurons in the BLA, while NB neurons that respond to appetitive and aversive stimuli may project to such neurons in the BLA.

Figure 3.

Proposed model representing how neurons in dorsal raphe nucleus (DRN) may convey valence information to BLA neurons. According to this model: DRN neurons that respond to aversive stimuli project to BLA neurons that respond to aversive stimuli only; DRN neurons that respond to aversive and appetitive stimuli project to BLA neurons also responsive to both types of stimuli.

Figure 4.

Proposed models representing how neurons in the ventral tegmental area (VTA) may convey valence information to BLA neurons. If VTA neurons are segregated by valence, they may project to similar neurons in the BLA (left). Alternatively, VTA neurons that respond to appetitive stimuli may project to BLA neurons responding to the same valence, while other VTA neurons that respond to both aversive and appetitive stimuli may project to neurons in the BLA also responding to both valence stimuli.

Figure 5.

Proposed experimental approaches to investigate how positive and negative valence stimuli modulate BLA neuronal projectors (A) and BLA neurons (B). To identify whether inputs into the BLA carry information about positive and negative valence, BLA projectors will be identified using opsin-assisted circuit dissection by using infusion of retrograde virus encoding Cre recombinase within the BLA and laser stimulation in the brain area projecting to the BLA. (A) When recording in the brain region(s) that projects to the BLA, during behaviors driven by aversive and appetitive learning, we will be able to identify neurons projecting to the BLA (expressing the opsin in a Cre-dependent manner) and that encode positive and/or negative valence. (B) Using the same approach while recording BLA neuronal activity during behaviors driven by aversive and appetitive learning, we can determine whether BLA neurons encoding positive and/or negative valence information receive projections from different inputs.