| First Author | Riondel P | Year | 2024 |
| Journal | J Neurosci | Volume | 44 |
| Issue | 22 | PubMed ID | 38684364 |
| Mgi Jnum | J:369860 | Mgi Id | MGI:7734604 |
| Doi | 10.1523/JNEUROSCI.2289-22.2024 | Citation | Riondel P, et al. (2024) Evidence for Two Subpopulations of Cerebrospinal Fluid-Contacting Neurons with Opposite GABAergic Signaling in Adult Mouse Spinal Cord. J Neurosci 44(22) |
| abstractText | Spinal cerebrospinal fluid-contacting neurons (CSF-cNs) form an evolutionary conserved bipolar cell population localized around the central canal of all vertebrates. CSF-cNs were shown to express molecular markers of neuronal immaturity into adulthood; however, the impact of their incomplete maturation on the chloride (Cl(-)) homeostasis as well as GABAergic signaling remains unknown. Using adult mice from both sexes, in situ hybridization revealed that a proportion of spinal CSF-cNs (18.3%) express the Na(+)-K(+)-Cl(-) cotransporter 1 (NKCC1) allowing intracellular Cl(-) accumulation. However, we did not find expression of the K(+)-Cl(-) cotransporter 2 (KCC2) responsible for Cl(-) efflux in any CSF-cNs. The lack of KCC2 expression results in low Cl(-) extrusion capacity in CSF-cNs under high Cl(-) load in whole-cell patch clamp. Using cell-attached patch clamp allowing recordings with intact intracellular Cl(-) concentration, we found that the activation of ionotropic GABA(A) receptors (GABA(A)-Rs) induced both depolarizing and hyperpolarizing responses in CSF-cNs. Moreover, depolarizing GABA responses can drive action potentials as well as intracellular calcium elevations by activating voltage-gated calcium channels. Blocking NKCC1 with bumetanide inhibited the GABA-induced calcium transients in CSF-cNs. Finally, we show that metabotropic GABA(B) receptors have no hyperpolarizing action on spinal CSF-cNs as their activation with baclofen did not mediate outward K(+) currents, presumably due to the lack of expression of G-protein-coupled inwardly rectifying potassium (GIRK) channels. Together, these findings outline subpopulations of spinal CSF-cNs expressing inhibitory or excitatory GABA(A)-R signaling. Excitatory GABA may promote the maturation and integration of young CSF-cNs into the existing spinal circuit. |
