Enhanced GABA_A receptor-mediated activity following activation of NMDA receptors in Cajal-Retzius cells in the developing mouse neocortex

Abstract

Cajal-Retzius (CR) cells are among the earliest generated population of neurons in the developing neocortex and have been implicated in regulating cortical lamination. In rodents, CR cells are transient, being present only up to 2–3 weeks after birth. Although previous electrophysiological studies have demonstrated the presence of NMDA and GABA_A receptors in CR cells, little is known about the functional properties of these receptors. Using whole-cell patch-clamp techniques in neocortical slices, we confirmed the presence of D-aminophosphonovaleric acid (APV)- and ifenprodil-sensitive NMDA receptors, and found that the functional expression of this receptor subtype is strain specific. The NMDA-induced response was consistently accompanied by overriding current transients that were blocked by APV and ifenprodil. In addition, bicuculline readily abolished these transients without affecting the NMDA-induced current response. The generation of these overriding current transients was dependent upon intracellular Ca²⁺ and was prevented by dialysis with the high-affinity Ca²⁺-chelator BAPTA. Overall, this study uncovered a synergistic interaction between these receptors, whereby activation of NMDA receptors leads to enhanced GABA_A receptor-mediated activity through a Ca²⁺-dependent mechanism.