Linden D J
Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
J Neurophysiol. 1998 Jun;79(6):3151-6. doi: 10.1152/jn.1998.79.6.3151.
Cerebellar long-term potentiation (LTP) is a use-dependent increase in the strength of the granule cell-Purkinje neuron synapse that occurs after brief stimulation of granule cell axons at 2-8 Hz. Previous work has shown that cerebellar LTP also may be seen when synaptic currents are evoked in granule cell-glial cell pairs in culture. This finding suggests a model in which cerebellar LTP is expressed presynaptically and therefore may be detected by either neuronal or glial postsynaptic cells. However, synaptic currents evoked in both granule cell-glial cell pairs and granule cell-Purkinje neuron pairs in culture are mediated primarily by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate receptors, raising the possibility that cerebellar LTP might be expressed postsynaptically in both glial cells and Purkinje neurons in a similar manner. To address this question, glutamate transport currents were recorded in granule cell-glial cell pairs in culture by pharmacological isolation. These currents were increased by substitution of internal Cl with NO3 and were blocked by -pyrrolidine-2,4-dicarboxylate, both characteristics of the major cloned Bergmann glial cell glutamate transporter, EAAT1. After acquisition of baseline responses, LTP of isolated transport current was evoked by stimulation at 4 Hz (100 pulses) and could be blocked by removal of external Ca during this stimulation. The expression of LTP was associated with a decrease in the rate of synaptic failures and a decrease in the degree of paired-pulse facilitation. These findings, when taken together with the previous observation that both Purkinje neuron and glial AMPA/kainate responses can be used to detect cerebellar LTP, strongly suggest that the expression of cerebellar LTP is, at least in part, presynaptic. This strategy should also be useful in illuminating the locus of expression of other model systems of information storage such as hippocampal LTP/long-term depression.
小脑长时程增强（LTP）是颗粒细胞 - 浦肯野神经元突触强度的一种使用依赖性增加，它在以2 - 8赫兹的频率短暂刺激颗粒细胞轴突后出现。先前的研究表明，当在培养的颗粒细胞 - 神经胶质细胞对中诱发突触电流时，也可以观察到小脑LTP。这一发现提示了一种模型，其中小脑LTP在突触前表达，因此可以被神经元或神经胶质突触后细胞检测到。然而，在培养的颗粒细胞 - 神经胶质细胞对和颗粒细胞 - 浦肯野神经元对中诱发的突触电流主要由α - 氨基 - 3 - 羟基 - 5 - 甲基 - 4 - 异恶唑丙酸（AMPA）/海人藻酸受体介导，这增加了小脑LTP可能以类似方式在神经胶质细胞和浦肯野神经元的突触后表达的可能性。为了解决这个问题，通过药理学分离在培养的颗粒细胞 - 神经胶质细胞对中记录谷氨酸转运电流。用硝酸根替代内部氯离子可增加这些电流，并且它们被L - 吡咯烷 - 2,4 - 二羧酸阻断，这两者都是主要克隆的伯格曼神经胶质细胞谷氨酸转运体EAAT1的特征。在获得基线反应后，通过4赫兹（100个脉冲）的刺激诱发分离的转运电流的LTP，并且在此刺激期间去除外部钙离子可阻断该LTP。LTP的表达与突触失败率的降低和双脉冲易化程度的降低相关。这些发现与先前的观察结果（即浦肯野神经元和神经胶质AMPA /海人藻酸反应均可用于检测小脑LTP）相结合，强烈表明小脑LTP的表达至少部分是突触前的。这种策略在阐明其他信息存储模型系统（如海马LTP /长时程抑制）的表达位点方面也应该是有用的。
