Electrophysiological and Immunohistochemical Evidence for an Increase in GABAergic Inputs and HCN Channels in Purkinje Cells that Survive Developmental Ethanol Exposure.
Electrophysiological and Immunohistochemical Evidence for an Increase in GABAergic Inputs and HCN Channels in Purkinje Cells that Survive Developmental Ethanol Exposure.
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DOI：
10.1007/s12311-015-0651-2
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发表时间：
2015-08
期刊：
影响因子：
--
通讯作者：
Pierce DR
中科院分区：
文献类型：
--
作者：
Light KE;Hayar AM;Pierce DR
在大鼠出生后早期暴露于乙醇导致浦肯野细胞（PC）的显著死亡。PC死亡的程度、时间进程和小叶特异性在几项研究中得到了很好的表征。此外，显着减少攀爬纤维输入幸存的PC已被表征。本研究探讨是否进一步改变小脑皮质电路可能会发生作为一个结果，发展乙醇暴露。我们首先研究了在出生后13-15天的急性切片制备的PC的发射模式。虽然基本的放电频率没有显着改变，出生后4-6天用乙醇处理的大鼠幼崽的PC显示出显着增加的抑制性突触后电位（IPSC）和较大的Ih电流。我们进行了免疫荧光研究，以确定IPSC增加的可能原因。我们发现每个PC的篮状细胞数量显著增加了21%，并且与PC共定位的篮状细胞轴突膜的体积增加了近一倍。此外，我们发现与PC体积共定位的HCN 1通道体积显著增加（约147%）。因此，小脑皮质的生存有针对性的出生后乙醇暴露显着改变PC死亡后的发展。由此产生的小脑皮层回路是在显著增加的静息抑制下运行的。乙醇暴露后小脑回路发育的改变以及PC的显著损失可能导致接受小脑输入的其他脑区域的结构和功能的改变。
Ethanol exposures during the early postnatal period of the rat result in significant death of Purkinje cells (PCs). The magnitude, time-course, and lobular specificity of PC death have been well characterized in several studies. Additionally, significant reduction of climbing fiber inputs to the surviving PCs has been characterized. This study investigates whether further alterations to the cerebellar cortical circuits might occur as a result of developmental ethanol exposures. We first examined the firing pattern of PCs in acute slice preparations on postnatal days 13–15. While the basic firing frequency was not significantly altered, PCs from rat pups treated with ethanol on postnatal days 4–6 showed a significantly increased number of inhibitory postsynaptic potentials (IPSCs) and a larger Ih current. We conducted immunofluorescent studies to identify the probable cause of the increased IPSCs. We found a significant 21 % increase in the number of basket cells per PC and a near doubling of the volume of colocalized basket cell axonal membrane with PC. In addition, we identified a significant (~147 %) increase in HCN1 channel volume co-localized to PC volume. Therefore, the cerebellar cortex that survives targeted postnatal ethanol exposure is dramatically altered in development subsequent to PC death. The cerebellar cortical circuit that results is one that operates under a significant degree of increased resting inhibition. The alterations in the development of cerebellar circuitry following ethanol exposure, and the significant loss of PCs, could result in modifications of the structure and function of other brain regions that receive cerebellar inputs.
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影响因子：
2.7
作者：
Cameron, D. Bryant;Kasai, Kazue;Jiang, Yulan;Hu, Taofang;Saeki, Yoshinaga;Komuro, Hitoshi
通讯作者：
Komuro, Hitoshi
影响因子：
158.5
作者：
COURCHESNE, E;YEUNGCOURCHESNE, R;JERNIGAN, TL
通讯作者：
JERNIGAN, TL
影响因子：
2.6
作者：
Connor, PD;Sampson, PD;Barr, HM
通讯作者：
Barr, HM
影响因子：
2.5
作者：
DOBBING, J;SANDS, J
通讯作者：
SANDS, J
DOI：
10.1111/j.1530-0277.1998.tb03713.x
发表时间：
1998-08-01
影响因子：
3.2
作者：
Bäckman, C;West, JR;Palmer, MR
通讯作者：
Palmer, MR