Enhanced LTP of primary afferent neurotransmission in AMPA receptor GluR2-deficient mice

Dong ho Youn, Gordon Royle, Miloslav Kolaj, Bryce Vissel, Mirjana Randić

Research output: Contribution to journalArticlepeer-review

46 Scopus citations

Abstract

Ca2+-permeable-AMPA receptors (AMPARs) are expressed in the superficial dorsal horn (SDH, laminae I/II) of the spinal cord, the area involved in transmission and modulation of sensory information, including nociception. A possible role of Ca2+-permeable-AMPARs in synaptic strengthening has been suggested in postnatal DH cultures, but their role in the long-lasting activity-dependent synaptic plasticity of primary afferent neurotransmission in the adult mouse SDH has not been investigated. In the present study the role of Ca2+-permeable-AMPARs in the regulation of long-lasting synaptic plasticity, specifically long-term potentiation (LTP) and long-term depression (LTD) in the SDH, was investigated using mice deficient in AMPAR GluR2 subunit. We show here that the GluR2 mutants exhibited no changes in passive membrane properties, but a significant increase in rectification of excitatory postsynaptic currents, the finding suggesting increased expression of Ca2+-permeable-AMPARs. In the absence of GluR2, high-frequency stimulation (HFS) of small-diameter primary afferent fibers induced LTP that is enhanced and non-saturating in the SDH at both primary afferent Aδ- and/or C-fibers monosynaptic and polysynaptic pathways, whereas neuronal excitability and paired-pulse depression were normal. The LTP could be induced in the presence of the NMDA receptor antagonist d-AP5, and L-type Ca2+ channel blockers, suggesting that Ca2+-permeable-AMPARs are sufficient to induce LTP in the SDH neurons of adult mouse spinal cord. In contrast, the induction of HFS-LTD is reduced in the SDH of GluR2 mutants. These results suggest an important role for AMPAR GluR2 subunit in regulating synaptic plasticity with potential relevance for long-lasting hypersensitivity in pathological states.

Original languageEnglish
Pages (from-to)158-167
Number of pages10
JournalPain
Volume136
Issue number1-2
DOIs
StatePublished - May 2008

Keywords

  • Ca-permeable-AMPA receptor
  • GluR2 knockout mice
  • LTP
  • Spinal cord

Fingerprint

Dive into the research topics of 'Enhanced LTP of primary afferent neurotransmission in AMPA receptor GluR2-deficient mice'. Together they form a unique fingerprint.

Cite this