Turner J P, Salt T E
Department of Visual Science, Institute of Ophthalmology, University College London, 11-43 Bath Street, EC1V 9EL, London, UK.
Neuroscience. 2000;100(3):493-505. doi: 10.1016/s0306-4522(00)00280-3.
Intracellular recordings were made from thalamocortical neurons in slices of rat dorsal lateral geniculate nucleus in vitro, where ionotropic glutamate receptors and ionotropic and metabotropic GABA receptors had been blocked. The activation of specific metabotropic glutamate receptors by exogenous agonists and by the electrical stimulation of the corticothalamic pathway was then assessed using selective antagonists. The specific group I agonist (S)-3, 5-dihydoxyphenylglycine and the non-selective agonist (1S, 3R)-1-aminocyclo-pentane-1,3-dicarboxylic acid both caused a concentration-dependent depolarization of membrane potential. These effects were associated with an increase in the apparent input resistance, and a more robust expression of both the depolarizing sag of the voltage response and the low-threshold Ca(2+) potential and an increase in thalamocortical neuron excitability. However, group I agonists selective for the mGlu5 receptor and agonists selective for group II and III receptors did not have these effects. Consequently, these data suggested that these actions were mediated specifically by the group I mGlu1 receptor. The activation of cortical fibres, with trains of 50 stimuli at 50Hz, resulted in a two-component depolarizing response. The first part of this synaptic response and the agonist-induced depolarization of membrane potential were depressed by the novel group I receptor antagonists LY367366 and LY367385, which are active at mGlu1 receptors. However, they were not blocked by 6-methyl-2-(phenylethyl)-pyridine, a highly selective mGlu5 receptor antagonist.Thus, the membrane potential depolarization of thalamocortical neurons caused either by exogenous agonists or by the stimulation of cortical fibres resulted from the specific activation of mGlu1 but not mGlu5 receptors. This result is consistent with the location of this receptor type on the distal dendrites of thalamocortical neurons in the dorsal lateral geniculate nucleus of the thalamus.
在体外对大鼠背外侧膝状核切片中的丘脑皮质神经元进行细胞内记录，此时离子型谷氨酸受体以及离子型和代谢型GABA受体已被阻断。然后使用选择性拮抗剂评估外源性激动剂和皮质丘脑通路电刺激对特定代谢型谷氨酸受体的激活作用。特异性I组激动剂（S）-3,5-二羟基苯甘氨酸和非选择性激动剂（1S,3R）-1-氨基环戊烷-1,3-二羧酸均引起膜电位的浓度依赖性去极化。这些效应与表观输入电阻增加、电压响应的去极化凹陷和低阈值Ca(2+)电位的更强烈表达以及丘脑皮质神经元兴奋性增加有关。然而，对mGlu5受体具有选择性的I组激动剂以及对II组和III组受体具有选择性的激动剂没有这些效应。因此，这些数据表明这些作用是由I组mGlu1受体特异性介导的。以50Hz的频率施加50次刺激的串刺激激活皮质纤维，会产生双成分去极化反应。这种突触反应的第一部分以及激动剂诱导的膜电位去极化被新型I组受体拮抗剂LY367366和LY367385抑制，这两种拮抗剂对mGlu1受体有活性。然而，它们未被6-甲基-2-（苯乙基）吡啶阻断，后者是一种高度选择性的mGlu5受体拮抗剂。因此，外源性激动剂或皮质纤维刺激引起的丘脑皮质神经元膜电位去极化是由mGlu1而非mGlu5受体的特异性激活所致。这一结果与该受体类型在丘脑背外侧膝状核中丘脑皮质神经元远端树突上的位置一致。
