Stem Cell Microenvironments and Beyond

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responses ranging from depolarizations that elicited spike firing (Fig. 5.4a) to
hyperpolarization from rest (Marichal et al. 2009 ; Reali et al. 2011 ). GABA-induced
depolarization in neurons is a common feature in the developing brain (Ben-Ari
2002 ; Ben-Ari and Spitzer 2010 ) and migrating neuroblasts in the SVZ and rostral
migratory stream (Wang et al. 2004 ). Both in the SVZ and the dentate gyrus, GABA
provides an excitatory drive to newborn neurons because of high activity of NKCC1
(Bordey 2007 ). As neurons mature, GABA action switches from excitation to inhi-
bition because down-regulation of NKCC1 and/or increase of KCC2 activity (Rivera
et  al. 1999 ; Ganguly et  al. 2001 ). Similarly, the excitatory action of GABA in
CSFcNs stems from a depolarized ECl because a predominance of NKCC1 over
KCC2 (Fig. 5.4b, c; Reali et al. 2011 ). In line with the idea that CFScNs may be at
different stages of maturation, cells hyperpolarized by GABA generally fired repeti-
tively -an electrophysiological phenotype of more differentiated neurons (Spitzer
et  al. 2004 ; Russo and Hounsgaard 1999 )- and have measurable KCC2 activity.
GABAA receptor activation induces an increase in intracellular Ca2+ that requires


Fig. 5.3 GABA signals on CC-contacting progenitors. (a) Current responses to a series of voltage
steps in a CC-contacting cell ( 1 ). The cell is dye coupled with neighbouring cells ( 2 ). Notice the
close proximity of GAD terminals to the cluster of dye coupled cells ( 2 , main panel and inset). (b)
Progenitors are depolarized by transient application of GABA (400 ms, 1 mM; (1). In some pro-
genitors GABA-induced inward currents (2) do not reverse at membrane potentials from −100 to
+20 mV (3). (c) In other clusters of progenitors, the depolarization induced by GABA ( 1 ) is gener-
ated by currents ( 2 ) that have clear reversal potentials ( 3 ). (a)2, confocal optical section. Scale bar
in (a)2: main panel, 20 μm; inset, 3 μm. Modified with permission from The Journal of Physiology
(Reali et al. 2011 )


N. Marichal et al.
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