Dataset Information

Divergent medial amygdala projections regulate approach-avoidance conflict behavior.

ABSTRACT: Avoidance of innate threats is often in conflict with motivations to engage in exploratory approach behavior. The neural pathways that mediate this approach-avoidance conflict are not well resolved. Here we isolated a population of dopamine D1 receptor (D1R)-expressing neurons within the posteroventral region of the medial amygdala (MeApv) in mice that are activated either during approach or during avoidance of an innate threat stimulus. Distinct subpopulations of MeApv-D1R neurons differentially innervate the ventromedial hypothalamus and bed nucleus of the stria terminalis, and these projections have opposing effects on investigation or avoidance of threatening stimuli. These projections are potently modulated through opposite actions of D1R signaling that bias approach behavior. These data demonstrate divergent pathways in the MeApv that can be differentially weighted toward exploration or evasion of threats.

SUBMITTER: Miller SM

PROVIDER: S-EPMC6446555 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Divergent medial amygdala projections regulate approach-avoidance conflict behavior.

Miller Samara M SM Marcotulli Daniele D Shen Angela A Zweifel Larry S LS

Nature neuroscience 20190225 4

Avoidance of innate threats is often in conflict with motivations to engage in exploratory approach behavior. The neural pathways that mediate this approach-avoidance conflict are not well resolved. Here we isolated a population of dopamine D1 receptor (D1R)-expressing neurons within the posteroventral region of the medial amygdala (MeApv) in mice that are activated either during approach or during avoidance of an innate threat stimulus. Distinct subpopulations of MeApv-D1R neurons differentiall ...[more]

PMID: 30804529

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Project description:Decisions under threat are crucial to survival and require integration of distinct situational features, such as threat probability and magnitude. Recent evidence from human lesion and neuroimaging studies implicated anterior hippocampus (aHC) and amygdala in approach-avoidance decisions under threat, and linked their integrity to cautious behavior. Here we sought to elucidate how threat dimensions and behavior are represented in these structures. Twenty human participants (11 female) completed an approach-avoidance conflict task during high-resolution fMRI. Participants could gather tokens under threat of capture by a virtual predator, which would lead to token loss. Threat probability (predator wake-up rate) and magnitude (amount of token loss) varied on each trial. To disentangle effects of threat features, and ensuing behavior, we performed a multifold parametric analysis. We found that high threat probability and magnitude related to BOLD signal in left aHC/entorhinal cortex. However, BOLD signal in this region was better explained by avoidance behavior than by these threat features. A priori ROI analysis confirmed the relation of aHC BOLD response with avoidance. Exploratory subfield analysis revealed that this relation was specific to anterior CA2/3 but not CA1. Left lateral amygdala responded to low and high, but not intermediate, threat probability. Our results suggest that aHC BOLD signal is better explained by avoidance behavior than by threat features in approach-avoidance conflict. Rather than representing threat features in a monotonic manner, it appears that aHC may compute approach-avoidance decisions based on integration of situational threat features represented in other neural structures.SIGNIFICANCE STATEMENT An effective threat anticipation system is crucial to survival across species. Natural threats, however, are diverse and have distinct features. To be able to adapt to different modes of danger, the brain needs to recognize these features, integrate them, and use them to modify behavior. Our results disclose the human anterior hippocampus as a likely arbiter of approach-avoidance decisions harnessing compound environmental information while partially replicating previous findings and blending into recent efforts to illuminate the neural basis of approach-avoidance conflict in humans.

Dataset Information

Divergent medial amygdala projections regulate approach-avoidance conflict behavior.

Publications

Divergent medial amygdala projections regulate approach-avoidance conflict behavior.

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