Synaptic Plasticity onto Dopamine Neurons Shapes Fear Learning

Marco Pignatelli, George Umanah, Sissi Palma Ribeiro, Rong Chen, Senthilkumar Karuppagounder, Hau Jie Yau, Stephen Eacker, Valina Dawson, Ted M Dawson, Antonello Bonci

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)425-440
Number of pages16
JournalNeuron
Volume93
Issue number2
DOIs
StatePublished - Jan 18 2017

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Keywords

  • dopamine
  • fear
  • memory
  • synaptic plasticity

ASJC Scopus subject areas

  • Neuroscience(all)

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