Amygdala-Dependent Molecular Mechanisms of the Tac2 Pathway in Fear Learning

Neuropsychopharmacology. 2016 Oct;41(11):2714-22. doi: 10.1038/npp.2016.77. Epub 2016 May 26.


Recently we determined that activation of the tachykinin 2 (Tac2) pathway in the central amygdala (CeA) is necessary and sufficient for the modulation of fear memories. The Tac2 pathway includes the Tac2 gene, which encodes the neuropeptide neurokinin B and its corresponding receptor neurokinin 3 receptor (NK3R). In this study, using Tac2-cre and Tac2-GFP mice, we applied a combination of in vivo (optogenetics) and multiple in vitro techniques to further explore the mechanisms of action within the Tac2 pathway. In transgenic mice that express ChR2 solely in Tac2 neurons, in vivo optogenetic stimulation of CeA Tac2-expressing neurons during fear acquisition enhanced fear memory consolidation and drove action potential firing in vitro. In addition, Tac2-CeA neurons were shown to co-express striatal-enriched protein tyrosine phosphatase, which may have an important role in regulating Nk3R signaling during fear conditioning. These data extend our current understanding for the underlying mechanism(s) for the role of the Tac2 pathway in the regulation of fear memory, which may serve as a new therapeutic target in the treatment of fear-related disorders.

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / genetics
  • Amygdala / drug effects
  • Amygdala / physiology*
  • Animals
  • Antipsychotic Agents / pharmacology
  • Channelrhodopsins
  • Conditioning, Classical / physiology
  • Fear*
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Learning / physiology*
  • Locomotion / genetics
  • Male
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Organophosphates / metabolism
  • Piperidines / pharmacology
  • Polymers / metabolism
  • Protein Kinase C-delta / metabolism
  • Protein Precursors / genetics*
  • Protein Precursors / metabolism
  • Protein Tyrosine Phosphatases, Non-Receptor / genetics
  • Protein Tyrosine Phosphatases, Non-Receptor / metabolism
  • Receptors, Neurokinin-3 / genetics
  • Receptors, Neurokinin-3 / metabolism
  • Signal Transduction / genetics*
  • Tachykinins / genetics*
  • Tachykinins / metabolism


  • Antipsychotic Agents
  • Channelrhodopsins
  • Organophosphates
  • Piperidines
  • Polymers
  • Protein Precursors
  • Receptors, Neurokinin-3
  • Tachykinins
  • preprotachykinin
  • tyrosine polyphosphate
  • Green Fluorescent Proteins
  • Protein Kinase C-delta
  • Protein Tyrosine Phosphatases, Non-Receptor
  • Ptpn5 protein, mouse
  • SR 142801