Modulation of network-driven, GABA-mediated giant depolarizing potentials by SDF-1alpha in the developing hippocampus

Dev Neurosci. 2008;30(4):285-92. doi: 10.1159/000112520. Epub 2007 Dec 12.

Abstract

Chemokine stromal cell-derived factor-1 (SDF-1, or CXCL12) plays an important role in brain development and functioning. Whole-cell patch clamp recordings were conducted on CA3 neurons in hippocampal slices prepared from neonatal rats between postnatal days 2 and 6 to study the modulatory effects of SDF-1alpha on network-driven, gamma-aminobutyric-acid-mediated giant depolarizing potentials (GDPs), a hallmark of the developing hippocampus. We found that SDF-1alpha, the only natural ligand for chemokine CXC motif receptor 4 (CXCR4), decreased GDP firing without significant effects on neuronal passive membrane properties in neonatal hippocampal neurons. The SDF-1alpha-mediated decrease in GDP firing was blocked by T140, a CXCR4 receptor antagonist, suggesting that SDF-1alpha modulates GDP firing via CXCR4. We also showed that endogenous SDF-1 exerts a tonic inhibitory action on GDPs in the developing hippocampus. As SDF-1/CXCR4 are highly expressed in the developing brain and GDPs are involved in activity-dependent synapse formation and functioning, the inhibitory action of SDF-1alpha on GDPs may reflect a potential mechanism for chemokine regulation of neural development in early neonatal life.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / physiology
  • Animals
  • Cells, Cultured
  • Chemokine CXCL12 / pharmacology
  • Chemokine CXCL12 / physiology*
  • Female
  • Hippocampus / cytology*
  • Hippocampus / embryology*
  • Hippocampus / physiology
  • Neural Inhibition / drug effects
  • Neural Inhibition / physiology
  • Neurons / cytology
  • Neurons / physiology*
  • Organ Culture Techniques
  • Patch-Clamp Techniques
  • Pregnancy
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, CXCR4 / physiology
  • gamma-Aminobutyric Acid / physiology*

Substances

  • Chemokine CXCL12
  • Cxcr4 protein, rat
  • Receptors, CXCR4
  • gamma-Aminobutyric Acid