Added astroglia promote greater synapse density and higher activity in neuronal networks
Added astroglia promote greater synapse density and higher activity in neuronal networks
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DOI：
10.1017/s1740925x07000440
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发表时间：
2007-01-01
影响因子：
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通讯作者：
Brewer, Gregory J.
中科院分区：
文献类型：
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作者：
Boehler, Michael D.;Wheeler, Bruce C.;Brewer, Gregory J.
已知星形胶质细胞可增强单个突触，但它们对神经网络的作用尚不清楚。在此，我们研究了添加星形胶质细胞或星形胶质细胞条件培养基对培养在微电极阵列上的大鼠海马神经元整个网络的影响。添加星形胶质细胞使自发放电频率增加近两倍，谷氨酸刺激的放电频率增加六倍，并且在浴槽中添加25μM谷氨酸时脱敏现象消失。星形胶质细胞条件培养基部分模拟了添加星形胶质细胞的效果。除添加谷氨酸外，爆发行为基本不受添加星形胶质细胞的影响。添加GABA（A）受体拮抗剂荷包牡丹碱也增加了放电频率，但在未添加和添加星形胶质细胞的网络之间存在更细微的差异。这表明未添加星形胶质细胞的网络受到了极大的抑制。在所有条件下，放电频率的对数 - 对数分布在三个数量级上很好地符合线性分布。添加星形胶质细胞的网络始终向更高的放电频率偏移。胶质纤维酸性蛋白（GFAP）免疫染色显示随着星形胶质细胞的添加呈线性增加，这也提高了神经元的存活率。添加星形胶质细胞后放电频率的增加与免疫反应性突触素斑点增加1.7倍相关，并且GABA（Aβ）斑点增加六倍，NMDA - R1斑点增加两倍，Glu - R1斑点增加两倍，受体聚集表明存在突触缩放。总之，这些结果表明添加星形胶质细胞可增加突触和受体的密度，并促进网络中许多元件的更高放电频率。除谷氨酸介导的传递外，这些效应可由胶质细胞条件培养基重现。
Astroglia are known to potentiate individual synapses, but their contribution to networks is unclear. Here we examined the effect of adding either astroglia or media conditioned by astroglia on entire networks of rat hippocampal neurons cultured on microelectrode arrays. Added astroglia increased spontaneous spike rates nearly two-fold and glutamate-stimulated spiking by six-fold, with desensitization eliminated for bath addition of 25 mu M glutamate. Astrocyte-conditioned medium partly mimicked the effects of added astroglia. Bursting behavior was largely unaffected by added astroglia except with added glutamate. Addition of the GABA(A) receptor antagonist bicuculline also increased spike rates but with more subtle differences between networks without or with added astroglia. This indicates that networks without added astroglia were inhibited greatly. In all conditions, the log-log distribution of spike rates fit well to linear distributions over three orders of magnitude. Networks with added astroglia shifted consistently toward higher spike rates. Immunostaining for GFAP revealed a linear increase with added astroglia, which also increased neuronal survival. The increased spike rates with added astroglia correlated with a 1.7-fold increase in immunoreactive synaptophysin puncta, and increases of six-fold for GABA(A beta), two-fold for NMDA-R1 and two-fold for Glu-R1 puncta, with receptor clustering that indicated synaptic scaling. Together, these results indicate that added astroglia increase the density of synapses and receptors, and facilitate higher spike rates for many elements in the network. These effects are reproduced by glia-conditioned media, with the exception of glutamate-mediated transmission.