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The ependyma of the adult spinal cord is a latent stem cell niche that is reactivated by spinal cord injury contributing new cells to the glial scar. The cellular events taking place in the early stages of the reaction of the ependyma to injury remain little understood. Ependymal cells are functionally heterogeneous with a mitotically active subpopulation lining the lateral domains of the central canal (CC) that are coupled via gap junctions. Gap junctions and connexin hemichannels are key regulators of the biology of neural progenitors during development and in adult neurogenic niches. Thus, we hypothesized that communication via connexins in the CC is developmentally regulated and may play a part in the reactivation of this latent stem cell niche after injury. To test these possibilities, we combined patch-clamp recordings of ependymal cells with immunohistochemistry for various connexins in the neonatal and the adult (P Ͼ 90) normal and injured spinal cord of male and female mice. We find that coupling among ependymal cells is downregulated as postnatal development proceeds but increases after injury, resembling the immature CC. The increase in gap junction coupling in the adult CC was paralleled by upregulation of connexin 26, which correlated with the resumption of proliferation and a reduction of connexin hemichannel activity. Connexin blockade reduced the injury-induced proliferation of ependymal cells. Our findings suggest that connexins are involved in the early reaction of ependymal cells to injury, representing a potential target to improve the contribution of the CC stem cell niche to repair.

The ependyma of the spinal cord is currently proposed as a latent neural stem cell niche. This chapter discusses recent knowledge on the developmental origin and nature of the heterogeneous population of cells that compose this stem cell microenviroment, their diverse physiological properties and regulation. The chapter also reviews relevant data on the ependymal cells as a source of plasticity for spinal cord repair.

Non-technical summary Neurogenesis is tightly regulated by epigenetic factors that assure the correct assembly of neural circuits. Neurotransmitters play a fundamental role in this type of control. We show that GABA signals on progenitors and immature neurones within a neurogenic niche around the central canal (CC) of the turtle spinal cord. GABA depolarized progenitors whereas the effect on immature neurones varied from excitation to inhibition. In both cell types GABA A receptor activation induced an increase in intracellular calcium. Our findings imply that GABAergic signalling around the CC shares fundamental properties with those in the embryo and adult neurogenic niches in the brain, suggesting that GABA is part of the mechanisms regulating the production and integration of neurones to already operational spinal circuits. Understanding the GABAergic modulation of progenitors and neuroblasts may provide useful clues about key mechanisms needed for functional neurogenesis in the spinal cord.Abstract The region that surrounds the central canal (CC) in the turtle spinal cord is a neurogenic niche immersed within already functional circuits, where radial glia expressing brain lipid binding protein (BLBP) behave as progenitors. The behaviour of both progenitors and neuroblasts within adult neurogenic niches must be regulated to maintain the functional stability of the host circuit. In the brain, GABA plays a major role in this kind of regulation but little is known about GABAergic signalling in neurogenic niches of the postnatal spinal cord. Here we explored the action of GABA around the CC of the turtle spinal cord by combining patch-clamp recordings of CC-contacting cells, immunohistochemistry for key components of GABAergic signalling and Ca 2+ imaging. Two potential sources of GABA appeared around the CC: GABAergic terminals and CC-contacting neurones. GABA depolarized BLBP + progenitors via GABA transporter-3 (GAT3) and/or GABA A receptors. In CC-contacting neurones, GABA A receptor activation generated responses ranging from excitation to inhibition. This functional heterogeneity appeared to originate from different ratios of activity of the Na + -K + -2Cl − co-transporter (NKCC1) and the K + -Cl − co-transporter (KCC2). In both progenitors and immature neurones, GABA induced an increase in intracellular Ca 2+ that required extracellular Ca 2+ and was blocked by the selective GABA A receptor antagonist gabazine. Our study shows that GABAergic signalling around the CC shares fundamental properties with those in the embryo and adult neurogenic niches, suggesting that GABA may be part of the mechanisms regulating the production and integration of neurones within operational spinal circuits in the turtle.