Neale S A, Salt T E
Department of Visual Science, Institute of Ophthalmology, University College London, 11-43 Bath Street, London EC1V 9EL, UK.
J Physiol. 2006 Dec 1;577(Pt 2):659-69. doi: 10.1113/jphysiol.2006.119073. Epub 2006 Sep 14.
Previous work has indicated that metabotropic glutamate receptors (mGluRs) modulate visual responses of superior colliculus (SC) neurones in vivo in a variety of ways, in a manner that can be dependent upon visual stimulus properties. How this occurs remains unclear. In this study we aimed to determine how activation of mGluR2 and mGluR3 receptors (Group II) might modulate visual responses, by using field potential and whole-cell patch clamp recording techniques in rat SC slice. Stimulation within the superficial layers of the SC, in the presence of ionotropic glutamate receptor antagonists, evoked IPSCs that were blocked by bicuculline indicating that they are mediated via GABAA receptors. It is likely that these IPSCs were of heterogeneous origin as they showed substantial variation in paired-pulse behaviour. Nevertheless, activation of Group II mGluRs with the group-selective agonist LY354740 (300 nM, bath application) resulted in a reduction of these IPSCs (to 56% of control amplitude), and this was associated with a decrease in paired-pulse depression. At the same concentration, LY354740 did not reduce the EPSC or field-EPSP evoked by stimulation of the retinal input to the SC. The effects of LY354740 on IPSCs were not mimicked by the mGluR3-selective agonist N-acetyl-aspartyl-glutamate (NAAG, 200-500 microM). Stimulation of IPSCs with trains of impulses (10 at 20 Hz) in order to mimic natural activation patterns resulted in sequences of IPSCs that were reduced in amplitude towards the end of the stimulus train. Application of the Group II antagonist LY341495 (100 nM) under these conditions resulted in an increase in later IPSCs in a third of neurones tested. These findings indicate that mGluR2 (but not mGluR3) can selectively modulate GABAergic inhibition in SC, probably via a presynaptic mechanism. Furthermore, these receptors may be activated by synaptically released transmitter during patterns of activation similar to those seen during visual processing. Thus mGluR2 receptors could have a function in activity-dependent modulation of inhibitory processing during visual responses.
先前的研究表明，代谢型谷氨酸受体（mGluRs）以多种方式在体内调节上丘（SC）神经元的视觉反应，其方式可能取决于视觉刺激特性。但这一过程如何发生仍不清楚。在本研究中，我们旨在通过使用大鼠SC脑片的场电位和全细胞膜片钳记录技术，确定mGluR2和mGluR3受体（II组）的激活如何调节视觉反应。在离子型谷氨酸受体拮抗剂存在的情况下，刺激SC的浅层可诱发IPSCs，荷包牡丹碱可阻断这些IPSCs，表明它们是通过GABAA受体介导的。这些IPSCs可能来源各异，因为它们在双脉冲行为上表现出很大差异。然而，用组选择性激动剂LY354740（300 nM，浴灌）激活II组mGluRs会导致这些IPSCs减少（降至对照幅度的56%），且这与双脉冲抑制的降低有关。在相同浓度下，LY354740不会降低刺激SC的视网膜输入所诱发的EPSC或场EPSP。mGluR3选择性激动剂N-乙酰天冬氨酰谷氨酸（NAAG，200 - 500 microM）不会模拟LY354740对IPSCs的作用。为了模拟自然激活模式，用一串冲动（20 Hz，10个）刺激IPSCs，结果导致IPSCs序列在刺激串末尾幅度减小。在这些条件下应用II组拮抗剂LY341495（100 nM），在三分之一的受试神经元中导致后期IPSCs增加。这些发现表明，mGluR2（而非mGluR3）可能通过突触前机制选择性调节SC中的GABA能抑制。此外，在类似于视觉处理过程中所见的激活模式期间，这些受体可能被突触释放的递质激活。因此，mGluR2受体可能在视觉反应期间抑制性处理的活动依赖性调节中发挥作用。
