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

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-1 alpha on network-driven, gamma-aminobutyricacidmediated giant depolarizing potentials (GDPs), a hallmark of the developing hippocampus. We found that SDF-1 alpha, 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-1 alpha-mediated decrease in GDP firing was blocked by T140, a CXCR4 receptor antagonist, suggesting that SDF-1 alpha 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-1 alpha on GDPs may reflect a potential mechanism for chemokine regulation of neural development in early neonatal life. Copyright (c) 2007 S. Karger AG, Basel.