Department of Visual Neuroscience, UCL Institute of Ophthalmology, University College London, 11-43 Bath Street, London EC1V 9EL, United Kingdom.
Neuropharmacology. 2012 Mar;62(4):1695-9. doi: 10.1016/j.neuropharm.2011.11.015. Epub 2011 Dec 7.
Metabotropic glutamate subtype 1 (mGlu1) receptor is thought to play a role in synaptic responses in thalamic relay nuclei. The aim of this study was to evaluate the positive allosteric modulator (PAM) Ro67-4853 as a tool to modulate thalamic mGlu1 receptors on single thalamic neurones in vivo. Ro67-4853, applied by iontophoresis onto ventrobasal thalamus neurones of urethane-anaesthetised rats, selectively enhanced responses to the agonist (S)-3,5-dihydroxy-phenylglycine (DHPG), an effect consistent with mGlu1 potentiation. The PAM was also able to enhance maintained responses to 10 Hz trains of sensory stimulation of the vibrissae, but had little effect on responses to single sensory stimuli. Thus Ro67-4853 appears to be a highly selective tool that can be useful in investigating how mGlu1 receptor potentiation can alter neural processing in vivo. Our results show the importance of mGlu1 in sensory processing and attention mechanisms at the thalamic level and suggest that positive modulation of mGlu1 receptors might be a useful mechanism for enhancing cognitive and attentional processes.
代谢型谷氨酸受体 1（mGlu1）亚型受体被认为在丘脑中继核的突触反应中发挥作用。本研究旨在评估正变构调节剂（PAM）Ro67-4853 作为一种工具，在体内调节单个丘脑神经元上的丘脑 mGlu1 受体。Ro67-4853 通过离子电渗作用应用于乌拉坦麻醉大鼠腹侧基底丘脑神经元，选择性增强对激动剂（S）-3,5-二羟基苯甘氨酸（DHPG）的反应，这与 mGlu1 增强作用一致。该 PAM 还能够增强对触须感觉刺激 10 Hz 串的持续反应，但对单个感觉刺激的反应影响不大。因此，Ro67-4853 似乎是一种高度选择性的工具，可用于研究 mGlu1 受体增强如何在体内改变神经处理。我们的结果表明，mGlu1 在丘脑水平的感觉处理和注意机制中很重要，并表明 mGlu1 受体的正变构调节可能是增强认知和注意力过程的有用机制。
