Spinal dorsal horn astrocytes release GABA in response to synaptic activation

Abstract

Astrocytes participate in neuronal signalling by releasing gliotransmitters in response to neurotransmitters. We investigated if astrocytes from the dorsal horn of the spinal cord of adult red-eared turtles (Trachemys scripta elegans) release GABA in response to glutamatergic receptor activation. For this, we developed a GABA sensor consisting of HEK cells expressing GABA receptors. By positioning the sensor recorded in the whole-cell patch-clamp configuration within the dorsal horn of a spinal cord slice, we could detect GABA in the extracellular space. Puff application of glutamate induced GABA release events with time courses that exceeded the duration of inhibitory postsynaptic currents by one order of magnitude. Because the events were neither affected by extracellular addition of nickel, cadmium and tetrodotoxin nor by removal of Ca , we concluded that they originated from non-neuronal cells. Immunohistochemical staining allowed the detection of GABA in a fraction of dorsal horn astrocytes. The selective stimulation of A∂ and C fibres in a dorsal root filament induced a Ca increase in astrocytes loaded with Oregon Green BAPTA. Finally, chelating Ca in a single astrocyte was sufficient to prevent the GABA release evoked by glutamate. Our results indicate that glutamate triggers the release of GABA from dorsal horn astrocytes with a time course compatible with the integration of sensory inputs.

Bi-Directional Communication Between Neurons and Astrocytes Modulates Spinal Motor Circuits

“…There is converging evidence that stimulating astrocytes pharmacologically, or ablating astrocytes with gliotoxins, reveals purinergic-dependent, glial-derived modulation of the spinal cord locomotor CPG (Dale and Gilday, 1996;Dale, 1998;Brown and Dale, 2000;Witts et al, 2012Witts et al, , 2015Acton and Miles, 2015;Acevedo et al, 2016;Acton and Miles, 2017;Acton et al, 2018;Rivera-Oliver et al, 2018). Although astrocytes in other CNS regions demonstrate the ability to utilize other transmitters, such as glutamate or GABA (Malarkey and Parpura, 2008;Christensen et al, 2018); there is a paucity of evidence to suggest that other gliotransmitters are involved in the astrocytic control of the locomotor CPG. In previous studies, antagonists of purinergic signaling were sufficient to block all the astrocytic effects on the locomotor network (Acton and Miles, 2015;Witts et al, 2015;Acton and Miles, 2017;Acton et al, 2018).…”

Allopregnanolone Enhances GABAergic Inhibition in Spinal Motor Networks

“…ALLO may act by positive allosteric modulation of agonist-induced receptor activation caused by ambient GABA. In this case, extrasynaptic GABA may arise from synaptically released GABA, and from GABA delivered by glial cells [ 34 ]. However, ALLO-induced tonic currents may also be caused by direct activation of GABA A -Rs, a mechanism that has been proposed for the bicuculline-sensitive current induced by the intravenous anesthetic thiopental [ 35 ].…”

Tetanus neurotoxin sensitive SNARE-mediated glial signaling limits motoneuronal excitability

“…Classic experiments revealed TeNT uptake into Schwann cells (Schwab and Thoenen, 1978) and glial cells exocytose substances influencing neural function possibly in a SNAREdependent manner (Carlsen and Perrier, 2014;Christensen et al, 2018;Christensen et al, 2013;Gucek et al, 2012;Schwarz et al, 2017;Verderio et al, 2012). We therefore wondered whether TeNT-LC targeted to glial cells could also affect motoneuronal function.…”