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

Synaptic Plasticity onto Dopamine Neurons Shapes Fear Learning.

Author information

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.

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

PMID:
28103482
DOI:
10.1016/j.neuron.2016.12.030
[Indexed for MEDLINE]
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