Dopamine and fear memory formation in the human amygdala

Andreas Frick,Allison Eriksson,Mark Lubberink,Johannes Björkstrand,Fredrik Åhs,Mats Fredrikson

doi:10.1038/s41380-021-01400-x

Andreas Frick, Allison Eriksson + Show 4 more

Open Access

https://doi.org/10.1038/s41380-021-01400-x

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Abstract

Learning which environmental cues that predict danger is crucial for survival and accomplished through Pavlovian fear conditioning. In humans and rodents alike, fear conditioning is amygdala-dependent and rests on similar neurocircuitry. Rodent studies have implicated a causative role for dopamine in the amygdala during fear memory formation, but the role of dopamine in aversive learning in humans is unclear. Here, we show dopamine release in the amygdala and striatum during fear learning in humans. Using simultaneous positron emission tomography and functional magnetic resonance imaging, we demonstrate that the amount of dopamine release is linked to strength of conditioned fear responses and linearly coupled to learning-induced activity in the amygdala. Thus, like in rodents, formation of amygdala-dependent fear memories in humans seems to be facilitated by endogenous dopamine release, supporting an evolutionary conserved neurochemical mechanism for aversive memory formation.

Highlights

Fear conditioning is an evolutionary shaped mechanism for aversive memory formation important for survival
In the frontal cortex, included here as a control region where we expected no decrease in BPND, we could not detect any change in BPND between baseline and post fear conditioning (mean change: −34.6%, 95% CI: −159.8% to 90.5%, t (17) = 0.54, P = 0.595) (Supplementary Fig. 3)
Complementing these analyses of mean dopamine release in each region, we performed within region voxel-wise analyses, revealing reduced BPND in bilateral amygdala clusters (Fig. 4) and in the striatum (Fig. 5)

Summary

Introduction

Fear conditioning is an evolutionary shaped mechanism for aversive memory formation important for survival. Neurochemical lesions to the dopamine system in the amygdala severely compromise fear learning [11, 12], and fear conditioning does not occur in genetically dopamine-deficient mice, but is restored with administration of the dopamine precursor L-DOPA [13]. Dopamine release seems both necessary [13] and sufficient [14] for fear conditioning in rodents, suggesting causation and implicating that human fear learning is dopaminedependent. No brain imaging study has directly evaluated if dopamine is released during amygdala-mediated associative learning or if the amount of dopamine released predicts learning strength

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