Evaluation of ambiguous associations in the amygdala by learning the structure of the environment

Abstract

Recognizing predictive relationships is critical for survival, but an understanding of the underlying neural mechanisms remains elusive. In particular it is unclear how the brain distinguishes predictive relationships from spurious ones when evidence about a relationship is ambiguous, or how it computes predictions given such uncertainty. To better understand this process we introduced ambiguity into an associative learning task by presenting aversive outcomes both in the presence and absence of a predictive cue. Electrophysiological and optogenetic approaches revealed that amygdala neurons directly regulate and track the effects of ambiguity on learning. Contrary to established accounts of associative learning however, interference from competing associations was not required to assess an ambiguous cue-outcome contingency. Instead, animals’ behavior was explained by a normative account that evaluates different models of the environment’s statistical structure. These findings suggest an alternative view on the role of amygdala circuits in resolving ambiguity during aversive learning.

Long time-scales in primate amygdala neurons support aversive learning

“…Albeit, the ITI here was of varying random duration and hence the next CS cannot be faithfully predicted from US offset, yet the coming CS is a complete predictor for the US. Together with the lack of preparatory (CR-like) behavior during the ITI, this supports the interpretation that it is not a mediated association, but rather a representation of trial structure and/or statistics of the environment that is represented in amygdala networks 27 .…”

“…The amygdala also plays a role in the acquisition of traceconditioning, where a temporal gap between the conditioned stimulus (CS) and the unconditioned stimulus (US) must be bridged [16][17][18][19][20] , and even in longer lags that were traditionally thought to be dependent on the hippocampus 21,22 . In addition, the amygdala plays a role in 2 nd -order conditioning [23][24][25] , that can be formed between the ITI itself and the CS 26 ; and even hold abstract representations of the trial structure beyond the CS-US relationship 27,28 . Further, the Amygdala can use its bi-directional connectivity with the anterior-cingulate-cortex (ACC) 29 .…”

Thalamic Regulation of Sucrose Seeking during Unexpected Reward Omission

“…While the neural encoding of such changes has long been attributed to the amygdala (Esber et al, 2015; Madarasz et al, 2016; Peck and Salzman, 2014; Sears et al, 2014; Stillman et al, 2015; Tye et al, 2008), emerging evidence suggests that the paraventricular nucleus of the thalamus (PVT) contributes to the regulation of emotional responses (Haight and Flagel, 2014; Hsu et al, 2014; Kirouac, 2015). PVT neurons are activated by contexts/cues associated with reward (Choi et al, 2010; Igelstrom et al, 2010; Li et al, 2016; Matzeu et al, 2015; Schiltz et al, 2007) or aversion (Beck and Fibiger, 1995; Do-Monte et al, 2015b; Penzo et al, 2015; Yasoshima et al, 2007; Zhu et al, 2016).…”

The Basolateral Amygdalae and Frontotemporal Network Functions for Threat Perception

“…For a better understanding of the central role of the AMG in threat perception, it is essential to distinguish the role of the different nuclei and map their specific connectivity profile (Hortensius et al, 2016a). Given the limitations of human imaging methods, the contribution of lesion studies is crucial (Adolphs, 2016; Madarasz et al, 2016). …”

“…The connections with the medial and orbital part of the prefrontal cortex underlies safety signaling, emotion regulation, and affective learning (Likhtik and Paz, 2015). The BLA are crucial in the perception and reaction to facial and bodily expressions and are particularly sensitive to ambiguity (Madarasz et al, 2016); this might especially be the case during a possible mismatch between these expressions.…”