Excitatory Synaptic Input to Hilar Mossy Cells under Basal and Hyperexcitable Conditions.
Excitatory Synaptic Input to Hilar Mossy Cells under Basal and Hyperexcitable Conditions.
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DOI：
10.1523/eneuro.0364-17.2017
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发表时间：
2017-11
期刊：
影响因子：
3.4
通讯作者：
Swanson GT
中科院分区：
文献类型：
--
作者：
Hedrick TP;Nobis WP;Foote KM;Ishii T;Chetkovich DM;Swanson GT
海马门状苔藓细胞（HMCs）通过苔藓纤维（MFs）和CA3锥体神经元侧支轴突的反向投射接受齿状颗粒细胞（DGCs）的谷氨酸能输入。这些兴奋性突触的许多基本特征尚未被详细描述，尽管它们可能与海马体认知加工和癫痫诱导的回路兴奋性适应有关。在这项研究中，我们比较了MF和CA3输入到年轻和成年小鼠hmc的突触前和突触后参数，并确定了在体外和体内海马高兴奋性模型中各自兴奋性输入的相对贡献。这两种类型的兴奋性突触都表现出适度的短期可塑性，与之前描述的MF - ca3锥体细胞突触相比，对hmc的MF输入表现出较低的成对脉冲（PP）和频率促进。与CA3-HMC突触相比，MF-HMC突触表现出更大振幅的单一兴奋性突触电流（EPSCs），含有突触后盐受体，NMDA/AMPA受体比值较低。体外诱导海马高兴奋性将大量但相对较弱的CA3-HMC连接转化为年轻小鼠（~ P20）中化合物EPSCs （cEPSCs）的非常大振幅自发爆发，在较小程度上，在成年小鼠（~ P70）中也是如此。海马内海钠酸盐注射几周后自发性癫痫小鼠的切片中也观察到CA3-HMC cEPSCs。在同步CA3活动期间，hmc的强兴奋代表了向DGCs产生显著兴奋性网络的途径，并且可能在产生癫痫网络中很重要。
Hilar mossy cells (HMCs) in the hippocampus receive glutamatergic input from dentate granule cells (DGCs) via mossy fibers (MFs) and back-projections from CA3 pyramidal neuron collateral axons. Many fundamental features of these excitatory synapses have not been characterized in detail despite their potential relevance to hippocampal cognitive processing and epilepsy-induced adaptations in circuit excitability. In this study, we compared pre- and postsynaptic parameters between MF and CA3 inputs to HMCs in young and adult mice of either sex and determined the relative contributions of the respective excitatory inputs during in vitro and in vivo models of hippocampal hyperexcitability. The two types of excitatory synapses both exhibited a modest degree of short-term plasticity, with MF inputs to HMCs exhibiting lower paired-pulse (PP) and frequency facilitation than was described previously for MF–CA3 pyramidal cell synapses. MF–HMC synapses exhibited unitary excitatory synaptic currents (EPSCs) of larger amplitude, contained postsynaptic kainate receptors, and had a lower NMDA/AMPA receptor ratio compared to CA3–HMC synapses. Pharmacological induction of hippocampal hyperexcitability in vitro transformed the abundant but relatively weak CA3–HMC connections to very large amplitude spontaneous bursts of compound EPSCs (cEPSCs) in young mice (∼P20) and, to a lesser degree, in adult mice (∼P70). CA3–HMC cEPSCs were also observed in slices prepared from mice with spontaneous seizures several weeks after intrahippocampal kainate injection. Strong excitation of HMCs during synchronous CA3 activity represents an avenue of significant excitatory network generation back to DGCs and might be important in generating epileptic networks.