Collège de France, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7241/Institut National de la Santé et de la Recherche Médicale U1050, 75231 Paris Cedex 05, France.
Proc Natl Acad Sci U S A. 2011 Nov 8;108(45):18442-6. doi: 10.1073/pnas.1107386108. Epub 2011 Oct 13.
Several recent findings have shown that neurons as well as astrocytes are organized into networks. Indeed, astrocytes are interconnected through connexin-formed gap junction channels allowing exchanges of ions and signaling molecules. The aim of this study is to characterize astrocyte network properties in mouse olfactory glomeruli where neuronal connectivity is highly ordered. Dye-coupling experiments performed in olfactory bulb acute slices (P16-P22) highlight a preferential communication between astrocytes within glomeruli and not between astrocytes in adjacent glomeruli. Such organization relies on the oriented morphology of glomerular astrocytes to the glomerulus center and the enriched expression of two astroglial connexins (Cx43 and Cx30) within the glomeruli. Glomerular astrocytes detect neuronal activity showing membrane potential fluctuations correlated with glomerular local field potentials. Accordingly, gap junctional coupling of glomerular networks is reduced when neuronal activity is silenced by TTX treatment or after early sensory deprivation. Such modulation is lost in Cx30 but not in Cx43 KO mice, indicating that Cx30-formed channels are the molecular targets of this activity-dependent modulation. Extracellular potassium is a key player in this neuroglial interaction, because (i) the inhibition of dye coupling observed in the presence of TTX or after sensory deprivation is restored by increasing K(+) and (ii) treatment with a K(ir) channel blocker inhibits dye spread between glomerular astrocytes. Together, these results demonstrate that extracellular potassium generated by neuronal activity modulates Cx30-mediated gap junctional communication between glomerular astrocytes, indicating that strong neuroglial interactions take place at this first relay of olfactory information processing.
最近的几项研究发现，神经元和星形胶质细胞都被组织成网络。事实上，星形胶质细胞通过间隙连接通道相互连接，允许离子和信号分子交换。本研究的目的是描述在神经元连接高度有序的小鼠嗅觉小球中星形胶质细胞网络的特性。在嗅球急性切片（P16-P22）中进行的染料偶联实验突出了小球内星形胶质细胞之间的优先通讯，而不是相邻小球内星形胶质细胞之间的通讯。这种组织依赖于小球星形胶质细胞对小球中心的定向形态以及小球内两种星形胶质细胞连接蛋白（Cx43 和 Cx30）的丰富表达。小球星形胶质细胞检测神经元活动，显示与小球局部场电位相关的膜电位波动。因此，当神经元活动被 TTX 处理或早期感觉剥夺沉默时，肾小球网络的缝隙连接偶联减少。在 Cx30 缺失而不是 Cx43 KO 小鼠中，这种调制丢失，表明 Cx30 形成的通道是这种活动依赖性调制的分子靶点。细胞外钾是这种神经胶质相互作用的关键因素，因为 (i) 在 TTX 存在或感觉剥夺后观察到的染料偶联抑制可以通过增加 K(+) 来恢复，并且 (ii) K(ir) 通道阻滞剂处理抑制肾小球星形胶质细胞之间的染料扩散。总之，这些结果表明，神经元活动产生的细胞外钾调节 Cx30 介导的肾小球星形胶质细胞之间的缝隙连接通讯，表明在嗅觉信息处理的这个第一中继中发生了强烈的神经胶质相互作用。
