Godwin D W, Van Horn S C, Eriir A, Sesma M, Romano C, Sherman S M
Department of Neurobiology, State University of New York, Stony Brook, New York 11794-5230, USA.
J Neurosci. 1996 Dec 15;16(24):8181-92. doi: 10.1523/JNEUROSCI.16-24-08181.1996.
Glutamate has an important neuromodulatory role in synaptic transmission through metabotropic glutamate receptors (mGluRs) linked to a variety of G-protein-coupled second messenger pathways. Activation of these receptors on relay cells in the lateral geniculate nucleus (LGN) with the agonist trans-(1S,3R)-1-amino-1, 3-cyclopentanedicarboxylic acid produces a membrane depolarization that inactivates the low-threshold Ca2+ spike, causing a transition from burst to tonic response mode. The excitatory effects of metabotropic receptor activation in the LGN appear to be produced through the receptors linked to phosphoinositide hydrolysis and apparently only through activation of the corticogeniculate pathway. Two mGluRs, mGluR1alpha (a splice variant of mGluR1) and mGluR5, are linked to the phosphoinositide system. We examined the localization of these receptors with affinity-purified, anti-peptide, polyclonal antibodies raised to the C-terminal region of each receptor protein. Under examination with the light microscope, we found that both types of receptors are present in the geniculate neuropil and in that of the overlying thalamic reticular nucleus, including the perigeniculate nucleus. We also examined the ultrastructural localization of immunolabel with the electron microscope, using a postembedding immunogold marker to identify terminals, dendrites, and somata that contain GABA. Label for the antibody directed against mGluR1alpha was primarily localized in the dendrites of relay cells, postsynaptic to various terminal types. Of these, terminal profiles normally associated with corticogeniculate inputs predominated, whereas retinal terminal profiles were scarce. Label for the antibody directed against mGluR5 label was prominent in inhibitory F2-terminal profiles associated with the retinal input to relay cells. In the perigeniculate nucleus, both mGluRs were localized to dendrites. The distribution of the two phosphoinositide-linked mGluRs in the LGN suggests very different functional roles for the two receptor types. We conclude from these data that mGluR1 appears to have a dominant role in corticogeniculate control of response mode through the feedback glutamatergic pathway from layer VI, whereas mGluR5 is positioned to affect retinogeniculate activation of relay cells through feed forward glomerular interactions.
谷氨酸通过与多种G蛋白偶联的第二信使途径相连的代谢型谷氨酸受体（mGluRs）在突触传递中发挥重要的神经调节作用。用激动剂反式-（1S，3R）-1-氨基-1，3-环戊烷二羧酸激活外侧膝状体核（LGN）中继细胞上的这些受体，会产生膜去极化，从而使低阈值Ca2+ 尖峰失活，导致从爆发式反应模式转变为紧张性反应模式。LGN中代谢型受体激活的兴奋作用似乎是通过与磷酸肌醇水解相关的受体产生的，并且显然仅通过皮质膝状体通路的激活产生。两种mGluRs，即mGluR1α（mGluR1的一种剪接变体）和mGluR5，与磷酸肌醇系统相关。我们用针对每种受体蛋白C末端区域制备的亲和纯化抗肽多克隆抗体检测了这些受体的定位。在光学显微镜下检查时，我们发现这两种类型的受体都存在于膝状体神经毡以及覆盖其上的丘脑网状核的神经毡中，包括膝状体周围核。我们还用电子显微镜检查了免疫标记的超微结构定位，使用包埋后免疫金标记来识别含有GABA的终末、树突和胞体。针对mGluR1α的抗体标记主要定位在中继细胞的树突中，这些树突是各种终末类型的突触后部位。其中，通常与皮质膝状体输入相关的终末形态占主导，而视网膜终末形态很少。针对mGluR5的抗体标记在与视网膜输入到中继细胞相关的抑制性F2终末形态中很突出。在膝状体周围核中，两种mGluRs都定位于树突。两种与磷酸肌醇相关的mGluRs在LGN中的分布表明这两种受体类型具有非常不同的功能作用。我们从这些数据得出结论，mGluR1似乎在通过来自VI层的反馈性谷氨酸能通路对反应模式的皮质膝状体控制中起主导作用，而mGluR5则通过前馈性肾小球相互作用影响中继细胞的视网膜膝状体激活。
