Spinal dorsal horn astrocytes release GABA in response to synaptic activation

Rasmus Kordt Christensen, Rodolfo Delgado-Lezama, Raúl E Russo, Barbara Lykke Lind, Emanuel Loeza Alcocer, Martin Fredensborg Rath, Gabriela Fabbiani, Nicole Schmitt, Martin Lauritzen, Anders Victor Petersen, Eva Meier Carlsen, Jean-François Perrier

29 Citationer (Scopus)

Abstract

KEY POINTS: GABA is an essential molecule for sensory information processing. It is usually assumed to be released by neurons. Here we show that in the dorsal horn of the spinal cord, astrocytes respond to glutamate by releasing GABA. Our findings suggest a novel role for astrocytes in somatosensory information processing.

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 GABAA 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 Ca2+ , 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 Ca2+ increase in astrocytes loaded with Oregon Green BAPTA. Finally, chelating Ca2+ 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.

OriginalsprogEngelsk
TidsskriftThe Journal of physiology
Vol/bind596
Udgave nummer20
Sider (fra-til)4983-4994
Antal sider12
ISSN0022-3751
DOI
StatusUdgivet - 2018
Udgivet eksterntJa

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