Synaptic kainate receptors tune oriens-lacunosum moleculare interneurons to operate at theta frequency
Synaptic kainate receptors tune oriens-lacunosum moleculare interneurons to operate at theta frequency
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DOI：
10.1523/jneurosci.1237-07.2007
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发表时间：
2007-09-05
影响因子：
5.3
通讯作者：
Cossart, Rosa
中科院分区：
文献类型：
--
作者：
Goldin, Miri;Epsztein, Jerome;Cossart, Rosa
海马体的 GABA 能中间神经元在行为相关网络振荡的产生中发挥着重要作用。在这种异质神经元群体中，生长抑素 (SOM) 阳性的东方缺损分子 (o-LM) 中间神经元非常引人注目，因为它们在体外和体内都被调整为以 θ 频率 (6-10 Hz) 运行。最近的研究表明，撞击 o-LM 中间神经元的谷氨酸能突触中有很大一部分是由红藻氨酸受体 (KA-R) 介导的。因此，在本研究中，我们测试了 KA-R 在以 θ 频率进行突触刺激期间在 o-LM 神经元中传递传入输入的假设。我们结合 SOM 增强绿色荧光蛋白 (EGFP) 小鼠海马切片的多束双光子钙成像，同时记录 SOM 细胞以及数百个神经元的活动，并进行有针对性的电生理记录和形态学分析，以描述特定细胞的形态功能特征。我们报告，EGFP 阳性 o-LM 神经元是中间神经元的唯一亚型，能够可靠地跟踪 θ 频率范围内肺泡的突触刺激。电生理记录揭示了与其他细胞类型相比，KA-R 对 o-LM 细胞的放电活动和对 θ 刺激的谷氨酸能反应的关键贡献。 o-LM 细胞在 theta 频率范围内的可靠激活不仅仅源于 KA-R 介导的突触后事件 (EPSPKA) 的较长动力学，而且可能源于 EPSPKA 与其内在活性膜特性之间的特定相互作用。这种通过远端投射 GABA 微电路通过 KA-R 对兴奋性输入进行优先处理可以在 θ 波段频率振荡中发挥关键作用。
GABAergic interneurons of the hippocampus play an important role in the generation of behaviorally relevant network oscillations. Among this heterogeneous neuronal population, somatostatin ( SOM)-positive oriens-lacunosum moleculare ( o-LM) interneurons are remarkable because they are tuned to operate at theta frequencies ( 6-10 Hz) in vitro and in vivo. Recent studies show that a high proportion of glutamatergic synapses that impinge on o-LM interneurons are mediated by kainate receptors ( KA-Rs). In the present study, we thus tested the hypothesis that KA-Rs transmit afferent inputs in o-LM neurons during synaptic stimulation at theta frequency. We combined multibeam two-photon calcium imaging in hippocampal slices from SOM-enhanced green fluorescent protein ( EGFP) mice, to record the activity of SOM cells as well as hundreds of neurons simultaneously, and targeted electrophysiological recordings and morphological analysis to describe the morphofunctional features of particular cells. We report that EGFP-positive o-LM neurons are the only subtype of interneuron that reliably follows synaptic stimulation of the alveus in the theta frequency range. Electrophysiological recordings revealed the crucial contribution of KA-Rs to the firing activity and to the glutamatergic response to theta stimuli in o-LM cells compared with other cell types. The reliable activation of o-LM cells in the theta frequency range did not simply result from the longer kinetics of KA-R-mediated postsynaptic events ( EPSPKA) but presumably from a specific interaction between EPSPKA and their intrinsic active membrane properties. Such preferential processing of excitatory inputs via KA-Rs by distally projecting GABAergic microcircuits could provide a key role in theta band frequency oscillations.