Mori Masahiro, Gerber Urs
Brain Research Institute, University of Zurich, Switzerland.
J Physiol. 2002 Nov 1;544(3):793-9. doi: 10.1113/jphysiol.2002.030163.
Interneurons are critical in regulating the excitability of principal cells in neuronal circuits, thereby modulating the output of neuronal networks. We investigated synaptically evoked inhibitory responses in CA3 pyramidal cells mediated by metabotropic glutamate receptors (mGluRs) expressed somatodendritically by interneurons. Although pharmacological activation of mGluRs in interneurons has been shown to enhance their excitability, the inability to record mGluR-mediated synaptic responses has precluded detailed characterization of mGluR function in hippocampal interneurons. We found that a single extracellular pulse in CA3 stratum pyramidale was sufficient to induce disynaptic inhibitory responses mediated by postsynaptic mGluRs of the interneurons in CA3 pyramidal cells of hippocampal slice cultures. The disynaptic inhibitory response followed a short-latency monosynaptic inhibitory response, and was observed at stimulus intensities evoking half-maximal monosynaptic IPSCs. Synergistic activation of mGluR1 and mGluR5 was required to induce the full inhibitory response. When recordings were obtained from interneurons in CA3 stratum radiatum or stratum oriens, a single extracellular stimulus induced a slow inward cationic current with a time course corresponding to the slow inhibitory response measured in pyramidal cells. DCG IV, a group II mGluR agonist, which specifically blocks synaptic transmission through mossy fibres, had no effect on mGluR-mediated synaptic responses in interneurons, suggesting that feed-forward inhibition via mossy fibres is not involved. Thus, postsynaptic mGluR1 and mGluR5 in hippocampal interneurons cooperatively mediate slow feedback inhibition of CA3 pyramidal cells. This mechanism may allow interneurons to monitor activity levels from populations of neighbouring principal cells to adapt inhibitory tone to the state of the network.
中间神经元在调节神经回路中主细胞的兴奋性方面至关重要，从而调节神经网络的输出。我们研究了由中间神经元树突体表达的代谢型谷氨酸受体（mGluRs）介导的CA3锥体细胞中的突触诱发抑制反应。尽管已证明中间神经元中mGluRs的药理学激活可增强其兴奋性，但无法记录mGluR介导的突触反应妨碍了对海马中间神经元中mGluR功能的详细表征。我们发现，在海马切片培养物的CA3锥体细胞中，CA3锥体层中的单个细胞外脉冲足以诱导由中间神经元的突触后mGluRs介导的双突触抑制反应。双突触抑制反应跟随短潜伏期单突触抑制反应，并在诱发半最大单突触IPSCs的刺激强度下观察到。需要mGluR1和mGluR5的协同激活来诱导完全抑制反应。当从CA3辐射层或原层的中间神经元进行记录时，单个细胞外刺激诱导了缓慢的内向阳离子电流，其时程与在锥体细胞中测量的缓慢抑制反应相对应。DCG IV，一种II组mGluR激动剂，它特异性阻断通过苔藓纤维的突触传递，对中间神经元中mGluR介导的突触反应没有影响，这表明不涉及通过苔藓纤维的前馈抑制。因此，海马中间神经元中的突触后mGluR1和mGluR5协同介导CA3锥体细胞的缓慢反馈抑制。这种机制可能允许中间神经元监测相邻主细胞群体的活动水平，以使抑制性调节适应网络状态。
