EXCITATORY AMINO-ACID PATHWAY FROM THE HIPPOCAMPUS TO THE PREFRONTAL CORTEX - CONTRIBUTION OF AMPA RECEPTORS IN HIPPOCAMPO-PREFRONTAL CORTEX TRANSMISSION
EXCITATORY AMINO-ACID PATHWAY FROM THE HIPPOCAMPUS TO THE PREFRONTAL CORTEX - CONTRIBUTION OF AMPA RECEPTORS IN HIPPOCAMPO-PREFRONTAL CORTEX TRANSMISSION
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DOI：
10.1111/j.1460-9568.1992.tb00154.x
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发表时间：
1992-12-01
影响因子：
3.4
通讯作者：
GLOWINSKI, J
中科院分区：
文献类型：
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作者：
JAY, TM;THIERRY, AM;GLOWINSKI, J
以前在大鼠身上的实验已经证明，CA1区和下丘脑投射到前额叶皮质，这一直接的单侧通路是兴奋的。本研究采用解剖学和电生理学方法，研究了前额叶皮质神经元对低频刺激海马区兴奋性反应的递质。用选择性D-[H-3]天冬氨酸逆行标记的方法识别前额叶皮质的谷氨酸能和/或天冬氨酸能传入纤维。单侧前额叶皮质前区微量注射D-[H-3]天冬氨酸可引起部分海马神经元的逆行标记。CA1区和下丘脑也有标记细胞，腹侧下丘和中间下丘脑有大量标记神经元。在第二系列实验中，对从海马区到前额叶皮质的兴奋性传递进行了药理学分析，以进一步证明谷氨酸和/或天冬氨酸参与了这一途径。谷氨酸受体亚型alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic酸和N-甲基-D-天冬氨酸的选择性激动剂可激活所有对刺激海马区有反应的前额叶皮质神经元，这些作用分别被6-氰基-7-硝基-2，3-二酮和2-氨基-5-膦戊酸选择性拮抗。CNQX可拮抗前额叶皮质神经元对单脉冲和双脉冲刺激海马区的兴奋反应。APV仅影响少数细胞的兴奋性反应。这些结果表明，海马区前额叶皮质的输入利用谷氨酸和/或天冬氨酸作为递质。尽管对海马区刺激作出反应的前额叶皮质神经元似乎同时具有AMPA和NMDA受体，但对海马-前额叶皮质通路的低频刺激主要通过AMPA受体激活皮质神经元。
Previous experiments in the rat have demonstrated that field CA1 and the subiculum project to the prefrontal cortex and that this direct unilateral pathway is excitatory. In the present study, anatomical and electrophysiological approaches were used to determine the transmitter mediating the excitatory responses in prefrontal cortex neurons to low-frequency stimulation of the hippocampus. The method of selective retrograde D-[H-3]aspartate labelling was used to identify putative glutamatergic and/or aspartatergic hippocampal afferent fibres to the prefrontal cortex. Unilateral microinjection of D-[H-3]aspartate into the prelimbic area of the prefrontal cortex resulted in the retrograde labelling of a fraction of hippocampal neurons. Some labelled cell bodies were distributed in field CA1 and the subiculum but larger numbers of neurons were detected in the ventral and intermediary subiculum. In a second series of experiments, the excitatory transmission from the hippocampus to the prefrontal cortex was pharmacologically analysed to provide further evidence for the involvement of glutamate and/or aspartate in the pathway. All prefrontal cortex neurons responding to the stimulation of the hippocampus were activated by selective agonists of the glutamate receptor subtypes alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) and N-methyl-D-aspartate (NMDA), and these effects were selectively antagonized by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and 2-amino-5-phosphonopentanoic acid (APV) respectively. Most of the excitatory responses of prefrontal cortex neurons to single and paired-pulse stimulation of the hippocampus were antagonized by CNQX. APV only affected the excitatory response in a few cells. These results suggest that the hippocampal input to the prefrontal cortex utilizes glutamate and/or aspartate as a transmitter. Even though prefrontal cortex neurons responding to the stimulation of the hippocampus appear to have both AMPA and NMDA receptors, low-frequency stimulation of the hippocampo-prefrontal cortex pathway activates cortical neurons mostly through AMPA receptors.