Gee C E, Woodhall G, Lacaille J C
Centre de Recherche en Sciences Neurologiques, Département de Physiologie, Université de Montréal, Montreal, Quebec H3C 3J7, Canada.
J Neurophysiol. 2001 Apr;85(4):1603-13. doi: 10.1152/jn.2001.85.4.1603.
Activation of metabotropic glutamate receptors (mGluRs) by agonists increases intracellular calcium levels (Ca(2+)) in interneurons of stratum oriens/alveus (OA) of the hippocampus. We examined the mechanisms that contribute to dendritic Ca(2+) increases in these interneurons during agonist activation of mGluRs and during synaptically evoked burst discharges, using simultaneous whole cell recordings and confocal Ca(2+) imaging in rat hippocampal slices. First, we found that the group I/II mGluR agonist 1S,3R-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD; 100 microM) increased dendritic Ca(2+) and depolarized OA interneurons. Dendritic Ca(2+) responses were correlated with membrane depolarizations, but Ca(2+) responses induced by ACPD were larger in amplitude than those elicited by equivalent somatic depolarization. Next, we used linescans to measure changes in dendritic Ca(2+) during synaptically evoked burst discharges and somatically elicited repetitive firing in disinhibited slices. Dendritic Ca(2+) signals and electrophysiological responses were stable over repeated trials. Peak Ca(2+) responses were linearly related to number and frequency of action potentials in burst discharges for both synaptic and somatic stimulation, but the slope of the relationship was steeper for responses evoked somatically. Synaptically evoked Ca(2+) rises and excitatory postsynaptic potentials were abolished by antagonists of ionotropic glutamate receptors. The group I/II mGluR antagonist S-alpha-methyl-4-carboxyphenylglycine (500 microM) produced a significant partial reduction of synaptically evoked dendritic Ca(2+) responses. The mGluR antagonist did not affect synaptically evoked burst discharges and did not reduce either Ca(2+) responses or burst discharges evoked somatically. Therefore ionotropic glutamate receptors appear necessary for synaptically evoked dendritic Ca(2+) responses, and group I/II mGluRs may contribute partially to these responses. Dendritic Ca(2+) rises mediated by both ionotropic and metabotropic glutamate receptors may be important for synaptic plasticity and the selective vulnerability to excitotoxicity of OA interneurons.
代谢型谷氨酸受体（mGluRs）激动剂激活海马体 Oriens/Alveus（OA）层中间神经元后，细胞内钙离子水平（Ca(2+)）会升高。我们利用大鼠海马体切片的全细胞同步记录和共聚焦钙离子成像技术，研究了在 mGluRs 激动剂激活以及突触诱发爆发式放电期间，导致这些中间神经元树突钙离子增加的机制。首先，我们发现 I/II 组 mGluR 激动剂 1S,3R-1-氨基环戊烷-1,3-二羧酸（ACPD；100 microM）可增加树突Ca(2+)并使 OA 中间神经元去极化。树突钙离子反应与膜去极化相关，但 ACPD 诱导的钙离子反应幅度大于同等体细胞去极化引发的反应。接下来，我们使用线扫描来测量在突触诱发爆发式放电以及在去抑制切片中体细胞诱发重复放电期间树突Ca(2+)的变化。在重复试验中，树突钙离子信号和电生理反应是稳定的。对于突触和体细胞刺激，峰值钙离子反应与爆发式放电中动作电位的数量和频率呈线性相关，但体细胞诱发反应的关系斜率更陡。离子型谷氨酸受体拮抗剂可消除突触诱发的Ca(2+)升高和兴奋性突触后电位。I/II 组 mGluR 拮抗剂 S-α-甲基-4-羧基苯甘氨酸（500 microM）可使突触诱发的树突钙离子反应显著部分降低。mGluR 拮抗剂不影响突触诱发的爆发式放电，也不减少体细胞诱发的钙离子反应或爆发式放电。因此，离子型谷氨酸受体似乎是突触诱发树突钙离子反应所必需的，I/II 组 mGluRs 可能部分参与这些反应。由离子型和代谢型谷氨酸受体介导的树突Ca(2+)升高可能对突触可塑性以及 OA 中间神经元对兴奋性毒性的选择性易感性很重要。
