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

doi:10.1113/jp276562

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

14 Citations (Scopus)

Abstract

KEY POINTS SUMMARY: 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. This article is protected by copyright. All rights reserved.

Original language	English
Journal	The Journal of Physiology
Volume	596
Issue number	20
Pages (from-to)	4983-4994
Number of pages	12
ISSN	0022-3751
DOIs	https://doi.org/10.1113/jp276562
Publication status	Published - 2018

Keywords

astrocyte
GABA
spinal cord

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title = "Spinal dorsal horn astrocytes release GABA in response to synaptic activation",

abstract = "KEY POINTS SUMMARY: 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. This article is protected by copyright. All rights reserved.",

keywords = "astrocyte, GABA, spinal cord",

author = "Christensen, {Rasmus Kordt} and Rodolfo Delgado-Lezama and Russo, {Ra{\'u}l E} and Lind, {Barbara Lykke} and Alcocer, {Emanuel Loeza} and Rath, {Martin Fredensborg} and Gabriela Fabbiani and Nicole Schmitt and Martin Lauritzen and Petersen, {Anders Victor} and Carlsen, {Eva Meier} and Jean-Fran{\c c}ois Perrier",

year = "2018",

doi = "10.1113/jp276562",

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T1 - Spinal dorsal horn astrocytes release GABA in response to synaptic activation

AU - Christensen, Rasmus Kordt

AU - Delgado-Lezama, Rodolfo

AU - Russo, Raúl E

AU - Lind, Barbara Lykke

AU - Alcocer, Emanuel Loeza

AU - Rath, Martin Fredensborg

AU - Fabbiani, Gabriela

AU - Schmitt, Nicole

AU - Lauritzen, Martin

AU - Petersen, Anders Victor

AU - Carlsen, Eva Meier

AU - Perrier, Jean-François

PY - 2018

Y1 - 2018

N2 - KEY POINTS SUMMARY: 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. This article is protected by copyright. All rights reserved.

AB - KEY POINTS SUMMARY: 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. This article is protected by copyright. All rights reserved.

KW - astrocyte

KW - GABA

KW - spinal cord

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DO - 10.1113/jp276562

M3 - Journal article

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SN - 0022-3751

VL - 596

SP - 4983

EP - 4994

JO - The Journal of Physiology

JF - The Journal of Physiology

IS - 20

ER -

Spinal dorsal horn astrocytes release GABA in response to synaptic activation

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