Salt T E, Jones H E, Copeland C S, Sillito A M
Visual Neuroscience, UCL Institute of Ophthalmology, London EC1V 9EL, United Kingdom.
Visual Neuroscience, UCL Institute of Ophthalmology, London EC1V 9EL, United Kingdom.
Neuropharmacology. 2014 Apr;79(100):405-11. doi: 10.1016/j.neuropharm.2013.12.016. Epub 2013 Dec 24.
As postsynaptic metabotropic subtype 1 (mGlu1) receptors are present in the thalamus, we have investigated the effect of potentiating and antagonising mGlu1 receptors on responses of thalamic neurones to noxious sensory stimulation. Extracellular recordings were made in vivo with multi-barrel iontophoretic electrodes from single neurones in the thalamus of urethane-anaesthetised rats. Responses to iontophoretic applications of the Group I mGlu agonist 3,5-dihydroxy-phenylglycine (DHPG) were selectively potentiated by co-application of the mGlu1 positive allosteric modulator Ro67-4853, whereas they were selectively reduced upon co-application of the mGlu1 receptor orthosteric antagonist LY367385. This indicates that thalamic DHPG responses are mediated primarily via mGlu1 receptors, consistent with the high postsynaptic levels of this receptor in the thalamus. Furthermore, potentiation of DHPG responses by Ro67-4853 were greater when the initial DHPG response was of a low magnitude. Ro67-4853 also potentiated responses of thalamic neurones to noxious thermal stimulation, whilst having little effect on the baseline activity of nociceptive neurones. By contrast, nociceptive responses were reduced by LY367385. In a further series of experiments we found that inactivation of somatosensory cortex by cooling resulted in a reduction of thalamic nociceptive responses. These results underline the importance of mGlu1 receptors in the processing of sensory information in the thalamus, particularly with respect to nociceptive responses. Furthermore, the involvement of mGlu1 receptors may reflect the activity of descending cortico-thalamic afferents.
由于丘脑存在突触后代谢型1（mGlu1）受体，我们研究了增强和拮抗mGlu1受体对丘脑神经元对伤害性感觉刺激反应的影响。在体内，使用多管离子电泳电极，从氨基甲酸乙酯麻醉大鼠丘脑的单个神经元进行细胞外记录。通过共同应用mGlu1正向变构调节剂Ro67-4853，I组mGlu激动剂3,5-二羟基苯甘氨酸（DHPG）的离子电泳应用反应被选择性增强，而在共同应用mGlu1受体正位拮抗剂LY367385时，反应被选择性降低。这表明丘脑DHPG反应主要通过mGlu1受体介导，这与该受体在丘脑中较高的突触后水平一致。此外，当最初的DHPG反应幅度较低时，Ro67-4853对DHPG反应的增强作用更大。Ro67-4853还增强了丘脑神经元对伤害性热刺激的反应，同时对伤害性神经元的基线活动影响很小。相比之下，LY367385降低了伤害性反应。在另一系列实验中，我们发现通过冷却使体感皮层失活会导致丘脑伤害性反应降低。这些结果强调了mGlu1受体在丘脑感觉信息处理中的重要性，特别是在伤害性反应方面。此外，mGlu1受体的参与可能反映了下行皮质-丘脑传入纤维的活动。
