Plasticity of metabotropic glutamate receptor-dependent long-term depression in the anterior cingulate cortex after amputation

J Neurosci. 2012 Aug 15;32(33):11318-29. doi: 10.1523/JNEUROSCI.0146-12.2012.

Abstract

Long-term depression (LTD) is a key form of synaptic plasticity important in learning and information storage in the brain. It has been studied in various cortical regions, including the anterior cingulate cortex (ACC). ACC is a crucial cortical region involved in such emotion-related physiological and pathological conditions as fear memory and chronic pain. In the present study, we used a multielectrode array system to map cingulate LTD in a spatiotemporal manner within the ACC. We found that low-frequency stimulation (1 Hz, 15 min) applied onto deep layer V induced LTD in layers II/III and layers V/VI. Cingulate LTD requires activation of metabotropic glutamate receptors (mGluRs), while L-type voltage-gated calcium channels and NMDA receptors also contribute to its induction. Peripheral amputation of the distal tail impaired ACC LTD, an effect that persisted for at least 2 weeks. The loss of LTD was rescued by priming ACC slices with activation of mGluR1 receptors by coapplying (RS)-3,5-dihydroxyphenylglycine and MPEP, a form of metaplasticity that involved the activation of protein kinase C. Our results provide in vitro evidence of the spatiotemporal properties of ACC LTD in adult mice. We demonstrate that tail amputation causes LTD impairment within the ACC circuit and that this can be rescued by activation of mGluR1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects
  • Amputation, Surgical*
  • Analysis of Variance
  • Animals
  • Biophysics
  • Biotinylation
  • Calcium Channel Blockers / pharmacology
  • Electric Stimulation / methods
  • Enzyme Inhibitors / pharmacology
  • Excitatory Amino Acid Agents / pharmacology
  • Glutamic Acid / pharmacology
  • Gyrus Cinguli / physiology*
  • In Vitro Techniques
  • Long-Term Synaptic Depression / drug effects
  • Long-Term Synaptic Depression / physiology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Nimodipine / pharmacology
  • Protein Transport / drug effects
  • Protein Transport / genetics
  • Receptors, Metabotropic Glutamate / metabolism*
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology*
  • Tail / innervation

Substances

  • Calcium Channel Blockers
  • Enzyme Inhibitors
  • Excitatory Amino Acid Agents
  • Receptors, Metabotropic Glutamate
  • metabotropic glutamate receptor type 1
  • Glutamic Acid
  • Nimodipine