Modulation of Network-Driven, GABA-Mediated Giant Depolarizing Potentials by SDF-1α in the Developing Hippocampus

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-1α on network-driven, γ-aminobutyric-acid-mediated giant depolarizing potentials (GDPs), a hallmark of the developing hippocampus. We found that SDF-1α, 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-1α-mediated decrease in GDP firing was blocked by T140, a CXCR4 receptor antagonist, suggesting that SDF-1α 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-1α on GDPs may reflect a potential mechanism for chemokine regulation of neural development in early neonatal life.