Astrocytes modulate thalamic sensory processing via mGlu2 receptor activation

C S Copeland, T M Wall, R E Sims, S A Neale, E Nisenbaum, H R Parri, T E Salt

Research output: Contribution to journalArticle

Abstract

Astrocytes possess many of the same signalling molecules as neurons. However, the role of astrocytes in information processing, if any, is unknown. Using electrophysiological and imaging methods, we report the first evidence that astrocytes modulate neuronal sensory inhibition in the rodent thalamus. We found that mGlu2 receptor activity reduces inhibitory transmission from the thalamic reticular nucleus to the somatosensory ventrobasal thalamus (VB): mIPSC frequencies in VB slices were reduced by the Group II mGlu receptor agonist LY354740, an effect potentiated by mGlu2 positive allosteric modulator (PAM) LY487379 co-application (30 nM LY354740: 10.0 ± 1.6% reduction; 30 nM LY354740 & 30 μM LY487379: 34.6 ± 5.2% reduction). We then showed activation of mGlu2 receptors on astrocytes: astrocytic intracellular calcium levels were elevated by the Group II agonist, which were further potentiated upon mGlu2 PAM co-application (300 nM LY354740: ratio amplitude 0.016 ± 0.002; 300 nM LY354740 & 30 μM LY487379: ratio amplitude 0.035 ± 0.003). We then demonstrated mGlu2-dependent astrocytic disinhibition of VB neurons in vivo: VB neuronal responses to vibrissae stimulation trains were disinhibited by the Group II agonist and the mGlu2 PAM (LY354740: 156 ± 12% of control; LY487379: 144 ± 10% of control). Presence of the glial inhibitor fluorocitrate abolished the mGlu2 PAM effect (91 ± 5% of control), suggesting the mGlu2 component to the Group II effect can be attributed to activation of mGlu2 receptors localised on astrocytic processes within the VB. Gating of thalamocortical function via astrocyte activation represents a novel sensory processing mechanism. As this thalamocortical circuitry is important in discriminative processes, this demonstrates the importance of astrocytes in synaptic processes underlying attention and cognition.
LanguageEnglish
Pages100-110
Number of pages11
JournalNeuropharmacology
Volume121
Early online date14 Apr 2017
DOIs
Publication statusPublished - 15 Jul 2017

Fingerprint

eglumetad
N-(4-(2-methoxyphenoxy)phenyl)-N-(2,2,2-trifluoroethylsulfonyl)pyrid-3-ylmethylamine
Thalamus
Astrocytes
Neurons
Vibrissae
Thalamic Nuclei
Automatic Data Processing
Neuroglia
Cognition
Rodentia
Calcium

Bibliographical note

© 2017 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Funding: BBSRC (BB/H530570/1 and BB/J017809/1); and Merck and Co.

Keywords

  • astrocyte
  • metabotropic glutamate receptor subtype 2
  • synaptic inhibition
  • thalamic reticular nucleus
  • thalamus

Cite this

Copeland, C S ; Wall, T M ; Sims, R E ; Neale, S A ; Nisenbaum, E ; Parri, H R ; Salt, T E. / Astrocytes modulate thalamic sensory processing via mGlu2 receptor activation. In: Neuropharmacology. 2017 ; Vol. 121. pp. 100-110.
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Astrocytes modulate thalamic sensory processing via mGlu2 receptor activation. / Copeland, C S; Wall, T M; Sims, R E; Neale, S A; Nisenbaum, E; Parri, H R; Salt, T E.

In: Neuropharmacology, Vol. 121, 15.07.2017, p. 100-110.

Research output: Contribution to journalArticle

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T1 - Astrocytes modulate thalamic sensory processing via mGlu2 receptor activation

AU - Copeland, C S

AU - Wall, T M

AU - Sims, R E

AU - Neale, S A

AU - Nisenbaum, E

AU - Parri, H R

AU - Salt, T E

N1 - © 2017 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). Funding: BBSRC (BB/H530570/1 and BB/J017809/1); and Merck and Co.

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