Dopamine-dependent QR2 pathway activation in ca1 interneurons enhances novel memory formation

Nathaniel L. Gould, Vijendra Sharma, Mohammad Hleihil, Sailendrakumar Kolatt Chandran, Orit David, Efrat Edry, Kobi Rosenblum

Research output: Contribution to journalArticlepeer-review


The formation of memory for a novel experience is a critical cognitive capacity. The ability to form novel memories is sensitive to age-related pathologies and disease, to which prolonged metabolic stress is a major contributing factor. Presently, we describe a dopamine-dependent redox modulation pathway within the hippocampus of male mice that promotes memory consolidation. Namely, following novel information acquisition, quinone reductase 2 (QR2) is suppressed by miRNA-182 (miR-182) in the CA1 region of the hippocampus via dopamine D1 receptor (D1R) activation, a process largely facilitated by locus coeruleus activity. This pathway activation reduces ROS generated by QR2 enzymatic activity, a process that alters the intrinsic properties of CA1 interneurons 3 h following learning, in a form of oxidative eustress. Interestingly, novel experience decreases QR2 expression predominately in inhibitory interneurons. Additionally, we find that in aged animals this newly described QR2 pathway is chronically under activated, resulting in miR-182 underexpression and QR2 overexpression. This leads to accumulative oxidative stress, which can be seen in CA1 via increased levels of oxidized, inactivated potassium channel Kv2.1, which undergoes disulfide bridge oligomerization. This newly described interneuron-specific molecular pathway lies alongside the known mRNA translation-dependent processes necessary for long-term memory formation, entrained by dopamine in CA1. It is a process crucial for the distinguishing features of novel memory, and points to a promising new target for memory enhancement in aging and age-dependent diseases.

Original languageEnglish
Pages (from-to)8698-8714
Number of pages17
JournalJournal of Neuroscience
Issue number45
StatePublished - 4 Nov 2020

Bibliographical note

Publisher Copyright:
© 2020 the authors


  • Dopamine
  • Hippocampus
  • Memory consolidation
  • Novelty
  • Protein synthesis
  • ROS
  • MicroRNAs/biosynthesis
  • Oxidative Stress
  • Interneurons/physiology
  • Male
  • Recognition, Psychology
  • CA1 Region, Hippocampal/growth & development
  • Signal Transduction/physiology
  • Aging/physiology
  • Memory/physiology
  • Reactive Oxygen Species/metabolism
  • Memory, Long-Term
  • Memory Consolidation/physiology
  • Mice, Inbred C57BL
  • Dopamine Antagonists/pharmacology
  • Dopamine/physiology
  • Shab Potassium Channels/metabolism
  • Fear/psychology
  • Animals
  • Mice
  • Quinone Reductases/physiology

ASJC Scopus subject areas

  • General Neuroscience


Dive into the research topics of 'Dopamine-dependent QR2 pathway activation in ca1 interneurons enhances novel memory formation'. Together they form a unique fingerprint.

Cite this