GABA mediates the network activity-dependent facilitation of axonal outgrowth from the newborn granule cells in the early postnatal rat hippocampus

Abstract

Neural network activity regulates the development of hippocampal newborn granule cells (GCs). Excitatory GABAergic input is known to be a key player in this regulation. Although calcium signaling is thought to be a downstream mediator of GABA, GABA-induced calcium signaling in newborn GCs is not well understood. We investigated Ca2+ signaling and its regulatory role in axon and dendrite outgrowth in newborn GCs identified in the organotypic slice culture of early postnatal rat hippocampus. Here, we report that hippocampal network activity can induce calcium transients (CaTs) in newborn GCs during the first post-mitotic week via GABAergic inputs. The GABA-induced CaTs were mediated mainly by L-type Ca2+ channels. Furthermore, we found that inhibiting any step in the signaling pathway, network activity ? GABA ? L-type Ca2+ channels, selectively suppressed the axonal outgrowth and pruning of newborn GCs, but not dendritic outgrowth. The GABAA receptor blocker bicuculline significantly suppressed axonal outgrowth, despite increasing network activity, thus indicating an essential role of GABAergic inputs. Therefore, we conclude that network activity-dependent GABAergic inputs open L-type Ca2+ channels and promote axonal outgrowth in newborn GC during the first post-mitotic week.