High firing rate of neonatal hippocampal interneurons is caused by attenuation of afterhyperpolarizing potassium currents by tonically active kainate receptors

J Neurosci. 2010 May 12;30(19):6507-14. doi: 10.1523/JNEUROSCI.4856-09.2010.


In the neonatal hippocampus, the activity of interneurons shapes early network bursts that are important for the establishment of neuronal connectivity. However, mechanisms controlling the firing of immature interneurons remain elusive. We now show that the spontaneous firing rate of CA3 stratum lucidum interneurons markedly decreases during early postnatal development because of changes in the properties of GluK1 (formerly known as GluR5) subunit-containing kainate receptors (KARs). In the neonate, activation of KARs by ambient glutamate exerts a tonic inhibition of the medium-duration afterhyperpolarization (mAHP) by a G-protein-dependent mechanism, permitting a high interneuronal firing rate. During development, the amplitude of the apamine-sensitive K+ currents responsible for the mAHP increases dramatically because of decoupling between KAR activation and mAHP modulation, leading to decreased interneuronal firing. The developmental shift in the KAR function and its consequences on interneuronal activity are likely to have a fundamental role in the maturation of the synchronous neuronal oscillations typical for adult hippocampal circuitry.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / physiology*
  • Animals
  • Animals, Newborn
  • CA3 Region, Hippocampal / growth & development*
  • CA3 Region, Hippocampal / physiology*
  • GTP-Binding Proteins / metabolism
  • Glutamic Acid / metabolism
  • In Vitro Techniques
  • Interneurons / physiology*
  • Membrane Potentials / physiology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neural Pathways / physiology
  • Patch-Clamp Techniques
  • Potassium / metabolism*
  • Receptors, Kainic Acid / deficiency
  • Receptors, Kainic Acid / genetics
  • Receptors, Kainic Acid / metabolism*


  • Gluk1 kainate receptor
  • Receptors, Kainic Acid
  • Glutamic Acid
  • GTP-Binding Proteins
  • Potassium