Hippocampal HECT E3 ligase inhibition facilitates consolidation, retrieval, and reconsolidation, and inhibits extinction of contextual fear memory

Neurobiol Learn Mem. 2020 Jan:167:107135. doi: 10.1016/j.nlm.2019.107135. Epub 2019 Dec 9.

Abstract

Ubiquitination is involved in synaptic plasticity and memory, but the involvement of HECT E3 ligases in these processes has not yet been established. Here, we bilaterally infused heclin, a specific inhibitor of some of these ligases, into the dorsal hippocampus of male Wistar rats that were trained in a contextual fear conditioning. Heclin improved short-term memory, consolidation, retrieval, and reconsolidation when administered immediately post training, prior to testing, or after memory reactivation, respectively. In addition, it impaired memory extinction when administered prior to a long reactivation session. Heclin infusion was also tested for locomotor activity and anxiety-like behavior in a circular arena, but no effect was seen. Taken together, these results indicate that HECT E3 ligases are involved in the modulation of fear memory.

Keywords: Fear conditioning; Heclin; Memory; Rat; Ubiquitin ligase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acrylamides / administration & dosage
  • Acrylamides / pharmacology
  • Animals
  • Conditioning, Classical / drug effects
  • Conditioning, Classical / physiology*
  • Enzyme Inhibitors / administration & dosage
  • Enzyme Inhibitors / pharmacology
  • Extinction, Psychological / drug effects
  • Extinction, Psychological / physiology
  • Fear / physiology*
  • Furans / administration & dosage
  • Furans / pharmacology
  • Hippocampus / drug effects
  • Hippocampus / physiology*
  • Male
  • Memory / drug effects
  • Memory / physiology*
  • Memory Consolidation / drug effects
  • Memory Consolidation / physiology
  • Mental Recall / drug effects
  • Mental Recall / physiology
  • Rats, Wistar
  • Ubiquitin-Protein Ligases / antagonists & inhibitors
  • Ubiquitin-Protein Ligases / physiology*

Substances

  • Acrylamides
  • Enzyme Inhibitors
  • Furans
  • heclin
  • Ubiquitin-Protein Ligases