GABA Regulates Dendritic Growth by Stabilizing Lamellipodia in Newly Generated Interneurons of the Olfactory Bulb

Abstract

The initial formation and growth of dendrites is a critical step leading to the integration of newly generated neurons into postnatal functional networks. However, the cellular mechanisms and extracellular signals regulating this process remain mostly unknown. By directly observing newborn neurons derived from the subventricular zone in culture as well as in olfactory bulb slices, we show that ambient GABA acting through GABA A receptors is essential for the temporal stability of lamellipodial protrusions in dendritic growth cones but did not interfere with filopodia dynamics. Furthermore, we provide direct evidence that ambient GABA is required for the proper initiation and elongation of dendrites by promoting the rapid stabilization of new dendritic segments after their extension. The effects of GABA on the initial formation of dendrites depend on depolarization and Ca 2ϩ influx and are associated with a higher stability of microtubules. Together, our results indicate that ambient GABA is a key regulator of dendritic initiation in postnatally generated olfactory interneurons and offer a mechanism by which this neurotransmitter drives early dendritic growth.

GABA and glutamate signaling: homeostatic control of adult forebrain neurogenesis

“…This increase in speed resulted in aberrant accumulation of neurons in the upper cortical layers. In the second study, Gascon et al (2006) showed that GABA regulates dendritic growth in cultured neuroblasts from the SVZ or in acute slices. In particular, bicuculline promoted the rapid stabilization of new dendritic segments.…”

Roles of Planar Cell Polarity Signaling in Maturation of Neuronal Precursor Cells in the Postnatal Mouse Olfactory Bulb

“…Previous studies identified several extracellular factors involved in the dendritogenesis of SVZ-derived OB interneurons, including GABA [58] and vascular endothelial growth factor (VEGF) [59]. Wnt5a, which likely activates the PCP signaling pathway, increases the neurite complexity of OB interneurons derived from the SVZ [35].…”

From progenitors to integrated neurons: Role of neurotransmitters in adult olfactory neurogenesis

“…Depolarizing GABA signalling modulates dendritic development of postnatally generated neurons in both hippocampus and olfactory bulb (Gascon et al, 2006;Ge et al, 2007). In the OB, incubation of SVZ-derived cell cultures from postnatal rat (at 1 day in vitro; 1 DIV) as well as OB slices, with the GABA A receptor antagonist bicuculline (but not GABA B and GABA C receptors antagonists), shows a reduction in dendritic complexity affecting primarily the number and length of primary dendrites.…”

“…In the OB, incubation of SVZ-derived cell cultures from postnatal rat (at 1 day in vitro; 1 DIV) as well as OB slices, with the GABA A receptor antagonist bicuculline (but not GABA B and GABA C receptors antagonists), shows a reduction in dendritic complexity affecting primarily the number and length of primary dendrites. GABA application has an opposite effect stimulating dendritic growth in new neurons (Gascon et al, 2006). This effect of GABA on dendrites development affects only immature neurons and is mediated by GABA A receptor depolarization and calcium influx through L-type voltage gated calcium channels.…”

“…This effect of GABA on dendrites development affects only immature neurons and is mediated by GABA A receptor depolarization and calcium influx through L-type voltage gated calcium channels. As the cell develops there is increased expression of the K + /Cl -cotransporter KCC2 and electrophysiological recordings as the mature chloride potentials establish, show a progressive shift toward a GABA-induced hyperpolarization of cultured SVZ-derived cells (Gascon et al, 2006). Accordingly, once the switch to hyperpolarizing GABA occurs, the action of bicuculline on dendritic development ceases (Gascon et al, 2006).…”