Altered long-term synaptic plasticity and kainate-induced Ca2+ transients in the substantia gelatinosa neurons in GLU(K6)-deficient mice

Brain Res Mol Brain Res. 2005 Dec 7;142(1):9-18. doi: 10.1016/j.molbrainres.2005.09.004. Epub 2005 Oct 10.

Abstract

Functional kainate receptors are expressed in the spinal cord substantia gelatinosa region, and their activation contributes to bi-directional regulation of excitatory synaptic transmission at primary afferent synapses with spinal cord substantia gelatinosa neurons. However, no study has reported a role(s) for kainate receptor subtypes in long-term synaptic plasticity phenomena in this region. Using gene-targeted mice lacking glutamate receptor 5 (GLU(K5)) or GLU(K6) subunit, we here show that GLU(K6) subunit, but not GLU(K5) subunit, is involved in the induction of long-term potentiation of excitatory postsynaptic potentials, evoked by two different protocols: (1) high-frequency primary afferent stimulation (100 Hz, 3 s) and (2) low-frequency spike-timing stimulation (1 Hz, 200 pulses). In addition, GLU(K6) subunit plays an important role in the expression of kainate-induced Ca2+ transients in the substantia gelatinosa. On the other hand, genetic deletion of GLU(K5) or GLU(K6) subunit does not prevent the induction of long-term depression. These results indicate that unique expression of kainate receptors subunits is important in regulating spinal synaptic plasticity and thereby processing of sensory information, including pain.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • 6-Cyano-7-nitroquinoxaline-2,3-dione / pharmacology
  • Age Factors
  • Animals
  • Benzoates / pharmacology
  • Cadmium Chloride / pharmacology
  • Calcium / metabolism*
  • Dose-Response Relationship, Radiation
  • Drug Interactions
  • Electric Stimulation / methods
  • Excitatory Amino Acid Agonists / pharmacology
  • Excitatory Amino Acid Antagonists / pharmacology
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / genetics
  • Excitatory Postsynaptic Potentials / physiology
  • Excitatory Postsynaptic Potentials / radiation effects
  • Glutamates / pharmacology
  • Glycine / analogs & derivatives
  • Glycine / pharmacology
  • In Vitro Techniques
  • Kainic Acid / pharmacology
  • Membrane Potentials / drug effects
  • Membrane Potentials / genetics
  • Membrane Potentials / physiology
  • Membrane Potentials / radiation effects
  • Mice
  • Mice, Knockout
  • Neuronal Plasticity / drug effects
  • Neuronal Plasticity / genetics
  • Neuronal Plasticity / physiology*
  • Neuronal Plasticity / radiation effects
  • Neurons / drug effects
  • Neurons / metabolism*
  • Patch-Clamp Techniques / methods
  • Protein Subunits / deficiency
  • Receptors, Kainic Acid / deficiency*
  • Substantia Gelatinosa / cytology*
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / pharmacology

Substances

  • Benzoates
  • Excitatory Amino Acid Agonists
  • Excitatory Amino Acid Antagonists
  • Glutamates
  • Protein Subunits
  • Receptors, Kainic Acid
  • 4-methylglutamic acid
  • alpha-methyl-4-carboxyphenylglycine
  • 6-Cyano-7-nitroquinoxaline-2,3-dione
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
  • Cadmium Chloride
  • Kainic Acid
  • Calcium
  • Glycine