Valence encoding in the amygdala influences motivated behavior

Abstract

The amygdala is critical for emotional processing and motivated behavior. Its role in these functions is due to its processing of the valence of environmental stimuli. The amygdala receives direct sensory input from sensory thalamus and cortical regions to integrate sensory information from the environment with aversive and/or appetitive outcomes. As many reviews have discussed the amygdala's role in threat processing and fear conditioning, this review will focus on how the amygdala encodes positive valence and the mechanisms that allow it to distinguish between stimuli of positive and negative valence. These findings are also extended to consider how valence encoding populations in the amygdala contribute to local and long-range circuits including those that integrate environmental cues and positive valence. Understanding the complexity of valence encoding in the amygdala is crucial as these mechanisms are implicated in a variety of disease states including anxiety disorders and substance use disorders.

Keywords: Amygdala; Learning; Valence.

Figure 1.. BLA Circuit Model.

Both basolateral amygdala (BLA) afferent and efferent projections contribute to valence encoding. The BLA receives cholinergic input from the basal forebrain (BF), serotonergic input from the dorsal raphe nucleus (DRN), and dopaminergic input from the ventral tegmental area (VTA). These projections respond to appetitive and aversive stimuli, which allows them to modulate valence encoding. Within the BLA, neuron ensembles encode positive versus negative valence and project to various downstream targets. For example, BLA projectors to the nucleus accumbens (NAc) encode positive valence, BLA projectors to portions of the central amygdala (CeA) encode negative valence, and projections from the BLA to the ventral hippocampus (vHPC) respond to valence-related cues.

Figure 2.. Cue-reward learning at thalamo-amygdala synapses.

Neurons in the lateral portion of the amygdala (LA) develop and maintain neural responses to a conditioned stimulus (CS) that has been paired with a reinforcing or aversive unconditioned stimulus (US). An initially weak pathway carrying sensory information about the CS (i.e. auditory cue) and strong afferents carrying US (i.e. sucrose, cocaine, footshock) information converge in the LA. Through Hebbian plasticity mechanisms, there is enhancement at the excitatory synapses carrying CS information. Specifically, animals that learn cue-reward associations have a larger AMPAR/NMDAR ratio at thalamo-amygdala synapses, indicative of increased glutamatergic synaptic strength. This strengthening is due to NMDAR-dependent increases in postsynaptic AMPAR number and/or function. In the case of positive valence, thalamo-amygdala synapses serve to encode and pair reward predictive cues with the reinforcing experience, thus giving the cue positive valence.