Amygdala-Midbrain Connections Modulate Appetitive and Aversive Learning

Elizabeth E Steinberg; Felicity Gore; Boris D Heifets; Madison D Taylor; Zane C Norville; Kevin T Beier; Csaba Földy; Talia N Lerner; Liqun Luo; Karl Deisseroth; Robert C Malenka

doi:10.1016/j.neuron.2020.03.016

Amygdala-Midbrain Connections Modulate Appetitive and Aversive Learning

Neuron. 2020 Jun 17;106(6):1026-1043.e9. doi: 10.1016/j.neuron.2020.03.016. Epub 2020 Apr 14.

Authors

Affiliations

¹ Nancy Pritzker Laboratory, Department of Psychiatry & Behavioral Sciences, Stanford University, Stanford, CA 94305, USA.
² Nancy Pritzker Laboratory, Department of Psychiatry & Behavioral Sciences, Stanford University, Stanford, CA 94305, USA; Departments of Bioengineering and Psychiatry and Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA.
³ Nancy Pritzker Laboratory, Department of Psychiatry & Behavioral Sciences, Stanford University, Stanford, CA 94305, USA; Department of Anesthesiology, Stanford University, Stanford, CA 94305, USA.
⁴ Nancy Pritzker Laboratory, Department of Psychiatry & Behavioral Sciences, Stanford University, Stanford, CA 94305, USA; Department of Biology and Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA.
⁵ Nancy Pritzker Laboratory, Department of Psychiatry & Behavioral Sciences, Stanford University, Stanford, CA 94305, USA; Brain Research Institute, University of Zurich, Zurich, Switzerland.
⁶ Departments of Bioengineering and Psychiatry and Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA.
⁷ Department of Biology and Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA.
⁸ Nancy Pritzker Laboratory, Department of Psychiatry & Behavioral Sciences, Stanford University, Stanford, CA 94305, USA. Electronic address: malenka@stanford.edu.

PMID: 32294466
DOI: 10.1016/j.neuron.2020.03.016

Abstract

The central amygdala (CeA) orchestrates adaptive responses to emotional events. While CeA substrates for defensive behaviors have been studied extensively, CeA circuits for appetitive behaviors and their relationship to threat-responsive circuits remain poorly defined. Here, we demonstrate that the CeA sends robust inhibitory projections to the lateral substantia nigra (SNL) that contribute to appetitive and aversive learning in mice. CeA→SNL neural responses to appetitive and aversive stimuli were modulated by expectation and magnitude consistent with a population-level salience signal, which was required for Pavlovian conditioned reward-seeking and defensive behaviors. CeA→SNL terminal activation elicited reinforcement when linked to voluntary actions but failed to support Pavlovian associations that rely on incentive value signals. Consistent with a disinhibitory mechanism, CeA inputs preferentially target SNL GABA neurons, and CeA→SNL and SNL dopamine neurons respond similarly to salient stimuli. Collectively, our results suggest that amygdala-nigra interactions represent a previously unappreciated mechanism for influencing emotional behaviors.

Keywords: Pavlovian; aversion; central amygdala; dopamine; instrumental; reinforcement learning; reward; salience; substantia nigra.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Appetitive Behavior / physiology*
Avoidance Learning / physiology*
Central Amygdaloid Nucleus / physiology*
Conditioning, Classical / physiology
Dopaminergic Neurons / physiology*
Emotions
GABAergic Neurons / physiology*
Mice
Neural Pathways
Reinforcement, Psychology
Reward
Substantia Nigra / cytology
Substantia Nigra / physiology*

Abstract

Publication types

MeSH terms

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