GABA mediates the network activity-dependent facilitation of axonal outgrowth from the newborn granule cells in the early postnatal rat hippocampus.
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 Ca(2+)  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 Ca(2+)  channels. Furthermore, we found that inhibiting any step in the signaling pathway, network activity → GABA → L-type Ca(2+)  channels, selectively suppressed the axonal outgrowth and pruning of newborn GCs, but not dendritic outgrowth. The GABA(A)  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 Ca(2+)  channels and promote axonal outgrowth in newborn GC during the first post-mitotic week.
Cell Physiology Lab., Department of Physiology and bioMembrane Plasticity Research Center, Seoul National University College of Medicine and Neuroscience Research Institute, Seoul National University Medical Research Center, 103 Daehak-ro, Jongno-gu, Seoul, 110-799, Korea.            Hanyang Biomedical Research Institute, Hanyang University, Seoul, Republic of Korea.
Hyunsu
H
Lee
Doyun
D
Lee
Chang-Hwan
CH
Park
Won-Kyung
WK
Ho
Suk-Ho
SH
Lee
D000818:Animals; D001369:Axons / Q000502:physiology*; D001640:Bicuculline / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000502:physiology; D020013:Calcium Signaling; D003712:Dendrites / Q000502:physiology; D058787:GABA-A Receptor Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000254:growth & development*; D009415:Nerve Net / Q000254:growth & development* / Q000502:physiology; D055495:Neurogenesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D020746:Calcium Channels, L-Type; D058787:GABA-A Receptor Antagonists; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid; D001640:Bicuculline