Ferraguti Francesco, Cobden Philip, Pollard Marie, Cope David, Shigemoto Ryuichi, Watanabe Masahiko, Somogyi Peter
MRC Anatomical Neuropharmacology Unit, Department of Pharmacology, Oxford University, Mansfield Road, OX1 3TH Oxford, UK.
Hippocampus. 2004;14(2):193-215. doi: 10.1002/hipo.10163.
In the hippocampal CA1 region, metabotropic glutamate subtype 1 (mGluR1) receptors have been implicated in a variety of physiological responses to glutamate, which include modulation of synaptic transmission and plasticity, as well as neuronal excitability and synchronization. The mGluR1alpha isoform is characteristically expressed only by nonprincipal cells, and it is particularly enriched in somatostatin (SS)-containing interneurons in stratum oriensalveus. Anatomical and physiological data have indicated the presence of mGluR1alpha in several distinct classes of interneurons with their somata located also in strata pyramidale, radiatum, and lacunosum moleculare. Each different interneuron subtype, as defined by functionally relevant criteria, including input/ output characteristics and expression of selective molecular markers, subserves distinct functions in local hippocampal circuits. We have investigated which of the different CA1 interneuron classes express mGluR1alpha by immunofluorescent labeling, combining antibodies to mGluR1alpha, calcium-binding proteins, and neuropeptides, and by intracellular labeling in vitro. Several types of interneuron that are immunopositive for mGluR1alpha each targeted different domains of pyramidal cells and included (1) O-LM inter-neurons, found to coexpress both SS and parvalbumin (PV); (2) interneurons with target selectivity for other interneurons, expressing vasoactive intestinal polypeptide (VIP) and/or the calcium-binding protein calretinin; (3) procholecystokinin-immunopositive interneurons probably non-basket and dendrite-targeting; and (4) an as-yet unidentified SS-immunoreactive but PV-immunonegative interneuron class, possibly corresponding to oriens-bistratified cells. Estimation of the relative proportion of mGluR1alpha-positive interneurons showed 43%, 46%, and 30% co-labeling with SS, VIP, or PV, respectively. The identification of the specific subclasses of CA1 interneurons expressing mGluR1alpha provides the network basis for assessing the contribution of this receptor to the excitability of the hippocampus.
在海马CA1区，代谢型谷氨酸受体1（mGluR1）参与了对谷氨酸的多种生理反应，包括调节突触传递和可塑性，以及神经元兴奋性和同步性。mGluR1α亚型仅在非主细胞中特异性表达，并且在海马齿状回分子层含生长抑素（SS）的中间神经元中特别丰富。解剖学和生理学数据表明，mGluR1α存在于几类不同的中间神经元中，它们的胞体也位于海马锥体层、辐射层和分子层。根据功能相关标准（包括输入/输出特性和选择性分子标记的表达）定义的每种不同的中间神经元亚型，在局部海马回路中发挥着不同的功能。我们通过免疫荧光标记，将针对mGluR1α、钙结合蛋白和神经肽的抗体结合起来，并通过体外细胞内标记，研究了不同的CA1中间神经元类别中哪些表达mGluR1α。几种对mGluR1α免疫阳性的中间神经元类型各自靶向锥体细胞的不同区域，包括：（1）O-LM中间神经元，发现其同时共表达SS和小白蛋白（PV）；（2）对其他中间神经元具有靶标选择性的中间神经元，表达血管活性肠肽（VIP）和/或钙结合蛋白钙视网膜蛋白；（3）前胆囊收缩素免疫阳性的中间神经元，可能是非篮状且靶向树突的；（4）一类尚未鉴定的SS免疫反应阳性但PV免疫阴性的中间神经元，可能对应于海马分子层双分层细胞。对mGluR1α阳性中间神经元相对比例的估计显示，分别有43%、46%和30%与SS、VIP或PV共标记。鉴定表达mGluR1α的CA1中间神经元的特定亚类，为评估该受体对海马兴奋性的贡献提供了网络基础。
