Coexistence of two forms of LTP in ACC provides a synaptic mechanism for the interactions between anxiety and chronic pain

Kohei Koga, Giannina Descalzi, Tao Chen, Hyoung-Gon Ko, Jinshan Lu, Shermaine Li, Junehee Son, TaeHyun Kim, Chuljung Kwak, Richard L Huganir, Ming-Gao Zhao, Bong-Kiun Kaang, Graham L Collingridge, Min Zhuo

Research output: Contribution to journalArticle (Academic Journal)peer-review

136 Citations (Scopus)
26 Downloads (Pure)

Abstract

Chronic pain can lead to anxiety and anxiety can enhance the sensation of pain. Unfortunately, little is known about the synaptic mechanisms that mediate these re-enforcing interactions. Here we characterized two forms of long-term potentiation (LTP) in the anterior cingulate cortex (ACC); a presynaptic form (pre-LTP) that requires kainate receptors and a postsynaptic form (post-LTP) that requires N-methyl-D-aspartate receptors. Pre-LTP also involves adenylyl cyclase and protein kinase A and is expressed via a mechanism involving hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. Interestingly, chronic pain and anxiety both result in selective occlusion of pre-LTP. Significantly, microinjection of the HCN blocker ZD7288 into the ACC in vivo produces both anxiolytic and analgesic effects. Our results provide a mechanism by which two forms of LTP in the ACC may converge to mediate the interaction between anxiety and chronic pain.

Original languageEnglish
Pages (from-to)377-389
Number of pages13
JournalNeuron
Volume85
Issue number2
Early online date31 Dec 2014
DOIs
Publication statusPublished - 21 Jan 2015

Keywords

  • Analgesics
  • Animals
  • Anti-Anxiety Agents
  • Anxiety
  • Chronic Pain
  • Gyrus Cinguli
  • Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
  • Long-Term Potentiation
  • Mice
  • Neurons
  • Pyrimidines
  • Receptors, Kainic Acid
  • Receptors, N-Methyl-D-Aspartate
  • Synaptic Transmission

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