67extracellular Ca2+, in both progenitors and immature neurons of the turtle CC (Reali
et al. 2011 ). These studies show that GABAergic signaling around the CC shares
fundamental properties with those in the embryo and adult neurogenic niches, sug-
gesting that GABA may be part of the mechanisms regulating the CC stem cell
niche. Future research has to solve the source of ambient GABA around the CC and
the functional role of GABAergic signaling on CC-contacting progenitors and
CSFcNs.
Another transmitter that has shown to have a role in the ependymal stem cell
niche is acetylcholine (Ach). The CC of rats is surrounded by cholin acetyl transfer-
ase (ChaT) fibers and Ach depolarizes ependymal cells and CSFcNs via activation of
α7- and non-α7 nicotinic Ach receptors (Corns et al. 2015 ). Furthermore, activation
of nicotinic receptors increases proliferation of ependymal cells both in vitro and
in vivo (Corns et al. 2015 ). This study suggests that cholinergic signaling may be a
key regulator of the CC stem cell niche. Interestingly, inflammation during experi-
mental autoimmune encephalomyelitis produces a decrease of ependymal cell pro-
liferation, an effect that is relieved by administration of nicotine (Gao et al. 2015 ).
ATP may be important to shape the properties of spinal progenitors, particularly
in the context of spinal cord injury. Purinergic signaling has an important role dur-
Fig. 5.4 GABA as a dual neurotransmitter: excitation and inhibition. (a) In some cases the GABA
induces a induced depolarization strong enough to generate spikes ( 1 , gramicidin perforated
patch). In a different sub-population of CSFcNs GABA generated a hyperpolarization that stops
firing ( 2 , gramicidin perforated patch). (b) Currents induced by GABA at −70 mV (1) in control
(top trace) and in the presence of bumetanide (20 μM, second trace from top). Notice that in the
presence of bumetanide, GABA generates an outward current, an effect that reversed upon wash
out (third trace from top). Blocakde of KCC2 with of furosemide (100 μM, fourth trace from top)
increased the amplitude of the inward GABA-induced current. The I/V plots of GABA-induced
currents shows the shifts in EGABA induced by bumetanide and furosemide (2). The scatter plot in 3
shows the changes in EGABA induced by bumetanide and furosemide for different cells. (c) Most
HuC/D cells ( 1 ) express NKCC1 ( 2 and 3 ). (d) Double immunohistochemistry for HuC/D ( 1 ) and
KCC2 ( 2 ). KCC2 is strongly expressed in neurons outside the CC region ( 1 – 3 arrows) whereas in
the ependyma is weakly expressed in some HuC/D+ cells located dorsally ( 1 – 3 , arrowheads). (c)
and (d), confocal optical sections. Scale bars: (c) and (d), 20 μm. Modified with permission from
The Journal of Physiology (Reali et al. 2011 )
5 Spinal Cord Stem Cells In Their Microenvironment: The Ependyma as a Stem Cell...