title: Synaptic Plasticity onto Dopamine Neurons Shapes Fear Learning.
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.
authors.affiliation: Intramural Research Program, Synaptic Plasticity Section, National Institute on Drug Abuse, Baltimore, MD 21224, USA.
authors.forename: Marco
authors.initials: M
authors.lastname: Pignatelli
authors.affiliation: 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.
authors.forename: George Kwabena Essien
authors.initials: GKE
authors.lastname: Umanah
authors.affiliation: Intramural Research Program, Synaptic Plasticity Section, National Institute on Drug Abuse, Baltimore, MD 21224, USA.
authors.forename: Sissi Palma
authors.initials: SP
authors.lastname: Ribeiro
authors.affiliation: 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.
authors.forename: Rong
authors.initials: R
authors.lastname: Chen
authors.affiliation: 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.
authors.forename: Senthilkumar Senthil
authors.initials: SS
authors.lastname: Karuppagounder
authors.affiliation: Intramural Research Program, Synaptic Plasticity Section, National Institute on Drug Abuse, Baltimore, MD 21224, USA.
authors.forename: Hau-Jie
authors.initials: HJ
authors.lastname: Yau
authors.affiliation: 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.
authors.forename: Stephen
authors.initials: S
authors.lastname: Eacker
authors.affiliation: 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.
authors.forename: Valina Lynn
authors.initials: VL
authors.lastname: Dawson
authors.affiliation: 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.
authors.forename: Ted Murray
authors.initials: TM
authors.lastname: Dawson
authors.affiliation: 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.
authors.forename: Antonello
authors.initials: A
authors.lastname: Bonci
mesh_terms: D000074183:ATPases Associated with Diverse Cellular Activities; D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001245:Association Learning / Q000502:physiology*; D001522:Behavior, Animal; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000502:physiology*; D005239:Fear; D055786:Gene Knockout Techniques; D061346:Laser Capture Microdissection; D007858:Learning / Q000502:physiology; D017774:Long-Term Potentiation / Q000502:physiology; D036881:Long-Term Synaptic Depression / Q000502:physiology; D051379:Mice; D009473:Neuronal Plasticity / Q000502:physiology*; D018408:Patch-Clamp Techniques; D018091:Receptors, AMPA / Q000378:metabolism; D013315:Stress, Psychological; D017557:Ventral Tegmental Area
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D018091:Receptors, AMPA; D000251:Adenosine Triphosphatases; C000591598:ATAD1 protein, mouse; D000074183:ATPases Associated with Diverse Cellular Activities; D004298:Dopamine
keywords: dopamine; fear; memory; synaptic plasticity