Synaptic Plasticity onto Dopamine Neurons Shapes Fear Learning

Marco Pignatelli; George Kwabena Essien Umanah; Sissi Palma Ribeiro; Rong Chen; Senthilkumar Senthil Karuppagounder; Hau-Jie Yau; Stephen Eacker; Valina Lynn Dawson; Ted Murray Dawson; Antonello Bonci

doi:10.1016/j.neuron.2016.12.030

Synaptic Plasticity onto Dopamine Neurons Shapes Fear Learning

Neuron. 2017 Jan 18;93(2):425-440. doi: 10.1016/j.neuron.2016.12.030.

Affiliations

¹ Intramural Research Program, Synaptic Plasticity Section, National Institute on Drug Abuse, Baltimore, MD 21224, USA.
² Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
³ Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
⁴ Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
⁵ Intramural Research Program, Synaptic Plasticity Section, National Institute on Drug Abuse, Baltimore, MD 21224, USA; Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Electronic address: antonello.bonci@nih.gov.

PMID: 28103482
DOI: 10.1016/j.neuron.2016.12.030

Abstract

Fear learning is a fundamental behavioral process that requires dopamine (DA) release. Experience-dependent synaptic plasticity occurs on DA neurons while an organism is engaged in aversive experiences. However, whether synaptic plasticity onto DA neurons is causally involved in aversion learning is unknown. Here, we show that a stress priming procedure enhances fear learning by engaging VTA synaptic plasticity. Moreover, we took advantage of the ability of the ATPase Thorase to regulate the internalization of AMPA receptors (AMPARs) in order to selectively manipulate glutamatergic synaptic plasticity on DA neurons. Genetic ablation of Thorase in DAT⁺ neurons produced increased AMPAR surface expression and function that lead to impaired induction of both long-term depression (LTD) and long-term potentiation (LTP). Strikingly, animals lacking Thorase in DAT⁺ neurons expressed greater associative learning in a fear conditioning paradigm. In conclusion, our data provide a novel, causal link between synaptic plasticity onto DA neurons and fear learning.

Keywords: dopamine; fear; memory; synaptic plasticity.

Published by Elsevier Inc.

MeSH terms

ATPases Associated with Diverse Cellular Activities
Adenosine Triphosphatases / genetics
Adenosine Triphosphatases / metabolism
Animals
Association Learning / physiology*
Behavior, Animal
Dopamine / metabolism*
Dopamine Plasma Membrane Transport Proteins / genetics
Dopamine Plasma Membrane Transport Proteins / metabolism
Dopaminergic Neurons / physiology*
Fear*
Gene Knockout Techniques
Laser Capture Microdissection
Learning / physiology
Long-Term Potentiation / physiology
Long-Term Synaptic Depression / physiology
Mice
Neuronal Plasticity / physiology*
Patch-Clamp Techniques
Receptors, AMPA / metabolism
Stress, Psychological*
Ventral Tegmental Area

Substances

Dopamine Plasma Membrane Transport Proteins
Receptors, AMPA
Adenosine Triphosphatases
ATAD1 protein, mouse
ATPases Associated with Diverse Cellular Activities
Dopamine