Loss of Transient Receptor Potential Ankyrin 1 Channel Deregulates Emotion, Learning and Memory, Cognition, and Social Behavior in Mice

Mol Neurobiol. 2017 Jul;54(5):3606-3617. doi: 10.1007/s12035-016-9908-0. Epub 2016 May 19.


The transient receptor potential ankyrin 1 (TRPA1) channel is a non-selective cation channel that helps regulate inflammatory pain sensation and nociception and the development of inflammatory diseases. However, the potential role of the TRPA1 channel and the underlying mechanism in brain functions are not fully resolved. In this study, we demonstrated that genetic deletion of the TRPA1 channel in mice or pharmacological inhibition of its activity increased neurite outgrowth. In vivo study in mice provided evidence of the TRPA1 channel as a negative regulator in hippocampal functions; functional ablation of the TRPA1 channel in mice enhanced hippocampal functions, as evidenced by less anxiety-like behavior, and enhanced fear-related or spatial learning and memory, and novel location recognition as well as social interactions. However, the TRPA1 channel appears to be a prerequisite for motor function; functional loss of the TRPA1 channel in mice led to axonal bundle fragmentation, downregulation of myelin basic protein, and decreased mature oligodendrocyte population in the brain, for impaired motor function. The TRPA1 channel may play a crucial role in neuronal development and oligodendrocyte maturation and be a potential regulator in emotion, cognition, learning and memory, and social behavior.

Keywords: Anxiolytic-like behavior; Cognition; Learning and memory; Myelination; Neuron differentiation; Social preference; Transient receptor potential ankyrin 1 channel.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amygdala / metabolism
  • Animals
  • Anxiety / metabolism
  • Axons / drug effects
  • Axons / metabolism
  • Behavior, Animal
  • Cell Differentiation / drug effects
  • Cell Line
  • Cognition* / drug effects
  • Emotions* / drug effects
  • Fear
  • Gene Deletion
  • Hippocampus / metabolism
  • Male
  • Memory* / drug effects
  • Mice
  • Motor Activity / drug effects
  • Myelin Sheath / metabolism
  • Neurites / drug effects
  • Neurites / metabolism
  • Oligodendroglia / drug effects
  • Oligodendroglia / metabolism
  • Social Behavior*
  • TRPA1 Cation Channel / deficiency
  • TRPA1 Cation Channel / metabolism*
  • Tretinoin / pharmacology


  • TRPA1 Cation Channel
  • Tretinoin