Central amygdala circuits in valence and salience processing

Abstract

Behavioral responses to environmental stimuli are dictated by the affective valence of the stimulus, good (positive valence) or bad (negative valence). These stimuli can innately elicit an affective response that promotes approach or avoidance behavior. In addition to innately valenced stimuli, valence can also be assigned to initially neutral stimuli through associative learning. A stimulus of a given valence can vary in salience depending on the strength of the stimulus, the underlying state of the animal, and the context of the stimulus presentation. Salience endows the stimulus with the ability to direct attention and elicit preparatory responses to mount an incentive-based motivated behavior. The central nucleus of the amygdala (CeA) has emerged as an early integration point for valence and salience detection to engage preparatory autonomic responses and behavioral posturing in response to both aversive and appetitive stimuli. There are numerous cell types in the CeA that are involved in valence and salience processing through a variety of connections, and we will review the recent progress that has been made in identifying these circuit elements and their roles in these processes.

Keywords: Central amygdala; Fear; Reward; Salience; Threat; Valence.

Figure 1. Cell types and connections of the central amygdala involved in valence and salience.

Numerous cell types defined by differential gene expression have been isolated and shown to contribute to valence and salience processing in the central amygdala (CeA). There are numerous reciprocal connections to other brain regions that have been identified as playing key roles in these processes. While there are known projections from the CeA to these regions, in many cases the cell types that project to these areas from the CeA or the cell types within these areas that receive CeA input remains to be resolved. The exception to this is projections from CeA-serotonin 2A receptor (Htr2a) cells which synapse onto the parabrachial nucleus (PBN) neurons in turn synapse on CeA-protein kinase C delta (PKCδ neurons [17]. SOM, somatostatin; CRF, corticotrophin releasing factor; Pnoc, prepronociceptin; Nts, neurotensin; Tac2, tachykinin 2; CeAl, lateral CeA; CeAm, medial CeA; CeAc, the central or capsular CeA; PVT, paraventricular thalamus; SNc, substantia nigra pars compacta; VTA, ventral tegmental area.

Figure 2. Types of valence and salience encoding in the CeA.

(A) Type I valence neurons show opposite responding to appetitive and aversive stimuli and do not respond to a CS. (B) Type 2 valence neurons respond positively to appetitive and aversive stimuli and acquire responses to the CS to encode the valence of the associated stimulus. (C) Type 1salience neurons respond in the same direction to either a positive or negatively valenced appetitive or aversive stimulus and acquire responses to encode the salience of the associated stimulus. (D) Type 2 salience encoding neurons do not respond to the US but respond in the same direction to the CS regardless of the valence of the US. (E) Type 3 salience neurons initially respond to the US but fully transition to responding to the CS following conditioning. Possible two different response types are represented with either solid lines or dotted lines.