Forti M, Michelson H B
Department of Pharmacology, State University of New York Health Science Center at Brooklyn, Brooklyn, New York 11203, USA.
J Neurophysiol. 1998 Jun;79(6):3229-37. doi: 10.1152/jn.1998.79.6.3229.
Dual intracellular recordings of hilar interneurons and CA3 pyramidal cells were performed in transverse slices of guinea pig hippocampus in the presence of the convulsant compound 4-aminopyridine (4-AP) and ionotropic glutamate receptor antagonists. Under these conditions, interneurons burst fire synchronously, producing synchronized inhibitory postsynaptic potentials (sIPSPs) in pyramidal cells. Three different hilar interneuron subpopulations that contributed to the sIPSP were identified based on their projection properties and morphology. These three types were pyramidal-like stellate interneurons, spheroid interneurons, and oviform interneurons. Physiologically, pyramidal-like stellate interneurons could be differentiated from the other interneuron subpopulations because they generated short synchronized bursts of action potentials coincident with the hyperpolarizing and depolarizing gamma-aminobutyric acid-A (GABAA)-mediated inhibitory postsynaptic potentials (IPSPs) recorded in pyramidal cells. The bursts in pyramidal-like stellate cells were abolished by theGABAA-receptor blocker, bicuculline. In contrast, spheroid interneurons of the dentate-hilus (D-H) border and oviform hilar interneurons exhibited prolonged bicuculline-resistant bursts that occurred coincident with the GABAB pyramidal cell sIPSPs. Pyramidal-like stellate interneurons likely did not contribute to the generation of synchronized GABAB responses in hippocampal pyramidal cells. Spheroid interneurons were unique among these subpopulations of interneurons in that the bicuculline-resistant bursts in spheroid interneurons were sustained by a synaptic depolarization that persisted in the presence of antagonists of ionotropic glutamate, GABAA and GABAB receptors [6-cyano-7-nitroquinoxaline-2,3-dione, 20 microM; 3-3(2-carboxipiperazine-4-yl)propyl-1-phosphonate, 20 microM; bicuculline, 10-15 microM; CGP 55845A, 20 microM]. This novel depolarizing potential reversed between -30 and 0 mV. No noticeable synaptic depolarization sustaining burst firing could be isolated in oviform interneurons, suggesting that firing in this interneuron subpopulation was synchronized by nonsynaptic mechanisms. The results of the present study indicate that the hilar inhibitory circuit is composed of at least three different subpopulations of interneurons, distinguishable by their morphological characteristics and synaptic inputs and outputs. These findings give further support to the hypothesis that there are distinct populations of interneurons producing GABAA and GABAB responses with defined functional roles within the hippocampal inhibitory circuit. Notably, we found that spheroid interneurons were unique among the hilar interneurons studied, in that the synchronized bursts observed in these cells are sustained by a novel ionotropic glutamate and GABA receptor-independent synaptic depolarization.
在惊厥性化合物4-氨基吡啶（4-AP）和离子型谷氨酸受体拮抗剂存在的情况下，对豚鼠海马横切片中的门区中间神经元和CA3锥体细胞进行了双细胞内记录。在这些条件下，中间神经元同步爆发放电，在锥体细胞中产生同步抑制性突触后电位（sIPSPs）。根据其投射特性和形态，确定了对sIPSP有贡献的三种不同的门区中间神经元亚群。这三种类型是锥体型星状中间神经元、球状中间神经元和卵形中间神经元。在生理上，锥体型星状中间神经元可以与其他中间神经元亚群区分开来，因为它们产生与在锥体细胞中记录到的超极化和去极化γ-氨基丁酸-A（GABAA）介导的抑制性突触后电位（IPSPs）同时出现的短同步动作电位爆发。锥体型星状细胞中的爆发被GABAA受体阻断剂荷包牡丹碱消除。相反，齿状回-门区（D-H）边界的球状中间神经元和卵形门区中间神经元表现出与GABAB锥体细胞sIPSPs同时出现的对荷包牡丹碱耐药的延长爆发。锥体型星状中间神经元可能对海马锥体细胞中同步GABAB反应的产生没有贡献。球状中间神经元在这些中间神经元亚群中是独特的，因为球状中间神经元中对荷包牡丹碱耐药的爆发由一种突触去极化维持，这种去极化在离子型谷氨酸、GABAA和GABAB受体拮抗剂[6-氰基-7-硝基喹喔啉-2,3-二酮，20微摩尔；3-3（2-羧基哌嗪-4-基）丙基-1-膦酸酯，20微摩尔；荷包牡丹碱，10-15微摩尔；CGP 55845A，20微摩尔]存在的情况下持续存在。这种新的去极化电位在-30至0 mV之间反转。在卵形中间神经元中未分离出明显的维持爆发放电的突触去极化，这表明该中间神经元亚群中的放电是通过非突触机制同步的。本研究结果表明，门区抑制性回路由至少三种不同的中间神经元亚群组成，可通过它们的形态特征以及突触输入和输出加以区分。这些发现进一步支持了这样的假说，即在海马抑制性回路中存在不同的中间神经元群体，它们产生具有明确功能作用的GABAA和GABAB反应。值得注意的是，我们发现球状中间神经元在所研究的门区中间神经元中是独特的，因为在这些细胞中观察到的同步爆发由一种新的不依赖离子型谷氨酸和GABA受体的突触去极化维持。
