Astrocytes modulate thalamic sensory processing via mGlu2 receptor activation

被引:26
作者
Copeland, C. S. [1 ,2 ]
Wall, T. M. [3 ]
Sims, R. E. [4 ]
Neale, S. A. [5 ]
Nisenbaum, E. [3 ]
Parri, H. R. [4 ]
Salt, T. E. [1 ]
机构
[1] UCL, Inst Ophthalmol, 11-43 Bath St, London EC1V 9EL, England
[2] St Georges Univ London, Cranmer Terrace, London SW17 0RE, England
[3] Eli Lilly & Co, 893 S Delaware St, Indianapolis, IN 46285 USA
[4] Aston Univ, Sch Life & Hlth Sci, Birmingham B4 7ET, W Midlands, England
[5] Neurexpert Ltd, Kemp House,152-160 City Rd, London EC1V 2NX, England
基金
英国生物技术与生命科学研究理事会;
关键词
Astrocyte; Metabotropic glutamate receptor subtype 2; Synaptic inhibition; Thalamus; Thalamic reticular nucleus; METABOTROPIC GLUTAMATE RECEPTORS; GROUP-II; PHARMACOLOGICAL CHARACTERIZATION; HIPPOCAMPAL ASTROCYTES; SYNAPTIC-TRANSMISSION; RETICULAR NUCLEUS; CA2+ OSCILLATIONS; GLIAL-CELLS; ADULT-RAT; INHIBITION;
D O I
10.1016/j.neuropharm.2017.04.019
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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 pM 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 mG1u2 PAM co-application (300 nM LY354740: ratio amplitude 0.016 0.002; 300 nM LY354740 & 30 pM 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 mG1u2 PAM effect (91 5% of control), suggesting the mGlu2 component to the Group II effect can be attributed to activation of mG1u2 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. (C) 2017 The Authors. Published by Elsevier Ltd.
引用
收藏
页码:100 / 110
页数:11
相关论文
共 69 条
[1]   Unique presynaptic and postsynaptic roles of Group II metabotropic glutamate receptors in the modulation of thalamic network activity [J].
Alexander, G. M. ;
Godwin, D. W. .
NEUROSCIENCE, 2006, 141 (01) :501-513
[2]  
[Anonymous], 1985, THALAMUS
[3]   The prefrontal cortex and flexible Behavior [J].
Barbas, Helen ;
Zikopoulos, Basilis .
NEUROSCIENTIST, 2007, 13 (05) :532-545
[4]   Group II and III metabotropic glutamate receptors contribute to different aspects of visual response processing in the rat superior colliculus [J].
Cirone, J ;
Salt, TE .
JOURNAL OF PHYSIOLOGY-LONDON, 2001, 534 (01) :169-178
[5]   Positive allosteric modulation reveals a specific role for mGlu2 receptors in sensory processing in the thalamus [J].
Copeland, C. S. ;
Neale, S. A. ;
Salt, T. E. .
JOURNAL OF PHYSIOLOGY-LONDON, 2012, 590 (04) :937-951
[6]  
Cox CL, 1999, J NEUROSCI, V19, P6694
[7]   Intrathalamic sensory connections mediated by the thalamic reticular nucleus [J].
Crabtree, JW .
CELLULAR AND MOLECULAR LIFE SCIENCES, 1999, 56 (7-8) :683-700
[8]   mGluR5 stimulates gliotransmission in the nucleus accumbens [J].
D'Ascenzo, Marcello ;
Fellin, Tommaso ;
Terunuma, Miho ;
Revilla-Sanchez, Raquel ;
Meaney, David F. ;
Auberson, Yves P. ;
Moss, Stephen J. ;
Haydon, Philip G. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (06) :1995-2000
[9]   Neuronal synchrony mediated by astrocytic glutamate through activation of extrasynaptic NMDA receptors [J].
Fellin, T ;
Pascual, O ;
Gobbo, S ;
Pozzan, T ;
Haydon, PG ;
Carmignoto, G .
NEURON, 2004, 43 (05) :729-743
[10]  
Flor PJ, 2002, ADV EXP MED BIOL, V513, P197