Modulation of network-driven, GABA-mediated giant depolarizing potentials by SDF-1alpha 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-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.
Kasiyanov
Alexander
A
Neurophysiology Laboratory, University of Nebraska Medical Center, Omaha, NE 68198-5880, USA.
Fujii
Nobutaka
N
Tamamura
Hirokazu
H
Xiong
Huangui
H
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000494:pharmacology / Q000502:physiology*; D005260:Female; D006624:Hippocampus / Q000166:cytology* / Q000196:embryology* / Q000502:physiology; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D019718:Receptors, CXCR4 / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D054377:Chemokine CXCL12; C486264:Cxcr4 protein, rat; D019718:Receptors, CXCR4; D005680:gamma-Aminobutyric Acid