Blockade of astrocyte metabolism causes delayed excitation as revealed by voltage-sensitive dyes in mouse brainstem slices
Blockade of astrocyte metabolism causes delayed excitation as revealed by voltage-sensitive dyes in mouse brainstem slices
复制标题
小鼠脑干切片中的电压敏感染料揭示星形胶质细胞代谢的阻断导致延迟兴奋
DOI：
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发表时间：
2003
影响因子：
2
通讯作者：
E. Speckmann
中科院分区：
文献类型：
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作者：
S. Hülsmann;H. Straub;D. Richter;E. Speckmann
摘要：氟乙酸酯可以阻断细胞代谢，并选择性地改变星形胶质细胞中的钾离子电导。在一个功能性的神经元网络与正在进行的活动，我们研究了这样一个封闭的星形胶质细胞代谢的氟乙酸钠对神经元信号传播的影响。从出生后第3-8天的小鼠尾侧髓质制备横向400 µm切片，其中包含接受腹侧呼吸组兴奋性突触输入的舌下神经核。通过使用电压敏感染料RH 795的光学成像测量该网络内的激发传播。一个464元件的光电二极管阵列允许在一小群细胞内快速记录电压变化。空间和时间分辨率分别提高到32 µm和1.27 ms。细胞膜电位水平的变化以荧光相对变化（ΔI/I）表示。从腹侧呼吸组向舌下神经核传播的神经元的刺激诱发兴奋在7.2± 0.6ms（n=6）后达到峰值。这种早期兴奋性反应的潜伏期与全细胞记录中刺激诱发的EPSP的时间过程一致。舌下神经核的平均荧光变化为−2.1±0.5×10−3（ΔI/I）。在1 mM氟乙酸盐中孵育后，早期去极化降低至对照的69.1±9.8%（n=6，p=0.034）。此外，氟乙酸盐诱导延迟的兴奋性反应，使得荧光强度在1秒内没有返回到基线。电压信号的传播速度和空间分布不受氟乙酸盐的影响。我们的研究结果表明，星形胶质细胞代谢的阻断损害快速突触传递，并诱导延迟兴奋，可能是由于神经元的复极减少和星形胶质细胞的持续去极化的组合。
Abstract.Fluoroacetate is known to block cell metabolism and to change potassium conductances selectively in astrocytes. In a functional neuronal network with ongoing activity, we investigated the effects of such a blockade of the astrocytic metabolism by fluoroacetate on neuronal signal propagation. Transverse 400-µm slices were prepared from the caudal medulla of mice of postnatal day 3–8, which contained the hypoglossal nucleus receiving excitatory synaptic input from the ventral respiratory group. Propagation of excitation within this network was measured by optical imaging using the voltage-sensitive dye RH 795. A 464-element photodiode array allowed fast recordings of voltage changes within a small population of cells. The spatial and temporal resolution was advanced to 32 µm and 1.27 ms, respectively. Changes of cellular membrane potential levels were expressed as relative changes of fluorescence (ΔI/I). Stimulus-evoked excitation of neurons propagating from the ventral respiratory group to the hypoglossal nucleus peaked after 7.2±0.6 ms (n=6). The latency of this early excitatory response is consistent with the time course of stimulus-evoked EPSPs in whole-cell recordings. Mean changes of fluorescence in the hypoglossal nucleus were −2.1±0.5×10−3 (ΔI/I). After incubation in 1 mM fluoroacetate, the early depolarization was reduced to 69.1±9.8% of control (n=6, p=0.034). Additionally, fluoroacetate induced a delayed excitatory response, such that fluorescence intensity did not return to baseline within 1 s. Propagation velocity and spatial distribution of the voltage signal were not affected by fluoroacetate. Our results suggest that blockade of astrocyte metabolism impairs fast synaptic transmission and induces a delayed excitation, probably resulting from the combination of reduced repolarization of neurons and persistent depolarization of astrocytes.
影响因子：
56.9
作者：
SMITH, JC;ELLENBERGER, HH;FELDMAN, JL
通讯作者：
FELDMAN, JL