Hyperexcitability of entorhinal cortex and hippocampus after application of aminooxyacetic acid (AOAA) to layer III of the rat medial entorhinal cortex in vitro.
Hyperexcitability of entorhinal cortex and hippocampus after application of aminooxyacetic acid (AOAA) to layer III of the rat medial entorhinal cortex in vitro.
复制标题
体外将氨氧乙酸（AOAA）应用于大鼠内侧内嗅皮质第三层后内嗅皮质和海马的过度兴奋。
DOI：
10.1152/jn.1996.76.5.2986
复制
发表时间：
1996
影响因子：
2.5
通讯作者：
Scharfman,HE
中科院分区：
文献类型：
--
作者：
Scharfman,HE
1.在体内将氨基氧乙酸（AOAA）注射到内嗅皮层中可引起急性癫痫发作和内侧内嗅皮层细胞丢失。为了了解这些影响，AOAA直接应用于内侧内嗅皮层的切片中含有内嗅皮层和海马。在内嗅皮层和海马进行细胞外和细胞内记录，以研究对角束刺激和自发活动的反应。2. AOAA通过微量移液管泄漏或压力喷射局部应用。诱发电位逐渐增加，在5分钟内的应用程序，特别是后期，负成分。诱发电位持续增加长达1小时，这些变化持续到实验的剩余时间（药物应用后长达5小时）。3.配对脉冲易化（100毫秒间隔）也增强后AOAA应用。将刺激频率增加到1-10 Hz进一步增加了诱发电位，并且在这种刺激几秒钟后发生多场电位。当此时停止刺激时，重复场电位自发发生1-2分钟。这些记录以及不同层的同时细胞外记录表明，内嗅神经元中发生了自发的同步活动。细胞内标记的皮质锥体细胞在自发和诱发场电位过程中去极化和放电。4. AOAA的作用被N-甲基-D-天冬氨酸（NMDA）受体拮抗剂D-氨基-5-膦酰基戊酸（D-APV; 25 μ M）的浴用或D-APV的局部应用可逆地阻断到内侧内嗅皮质。5.同时从内嗅皮层和海马细胞外记录表明，在第三层的自发同步活动往往是随后在几毫秒内的负场电位在终端区的perforant路径（层moleculare的齿状回和层陷窝moleculare的CA 1区）。在齿状回记录的细胞外电位对应于齿状回颗粒细胞的兴奋性突触后电位和动作电位。然而，CA 1区的细胞外电位很小，很少与CA 1锥体细胞的放电相关。6.结果表明，AOAA的应用导致了NMDA受体依赖性的增强内侧内嗅皮层神经元的诱发电位，这似乎是不可逆的。重复刺激可促进内嗅神经元的同步放电。放电侵入其他区域，如海马，表明癫痫发作活动可能会蔓延后AOAA注射体内。这些数据表明，AOAA可能是一个有用的工具，研究长期的变化，在NMDA受体功能，导致癫痫样活动和神经退行性变。
1. Injection of aminooxyacetic acid (AOAA) into the entorhinal cortex in vivo produces acute seizures and cell loss in medial entorhinal cortex. To understand these effects, AOAA was applied directly to the medial entorhinal cortex in slices containing both the entorhinal cortex and hippocampus. Extracellular and intracellular recordings were made in both the entorhinal cortex and hippocampus to study responses to angular bundle stimulation and spontaneous activity. 2. AOAA was applied focally by leak from a micropipette or by pressure ejection. Evoked potentials increased gradually within 5 min of application, particularly the late, negative components. Evoked potentials continued to increase for up to 1 h, and these changes persisted for the remainder of the experiment (up to 5 h after drug application). 3. Paired pulse facilitation (100-ms interval) was also enhanced after AOAA application. Increasing stimulus frequency to 1-10 Hz increased evoked potentials further, and after several seconds of such stimulation multiple field potentials occurred. When stimulation was stopped at this point, repetitive field potentials occurred spontaneously for 1-2 min. These recordings, and simultaneous extracellular recordings in different layers, indicated that spontaneous synchronous activity occurred in entorhinal neurons. Intracellularly labeled cortical pyramidal cells depolarized and discharged during spontaneous and evoked field potentials. 4. The effects of AOAA were blocked reversibly by bath application of the N-methyl-D-aspartate (NMDA) receptor antagonist D-amino-5-phosphonovalerate (D-APV; 25 microM) or focal application of D-APV to the medial entorhinal cortex. 5. Simultaneous extracellular recordings from the entorhinal cortex and hippocampus demonstrated that spontaneous synchronous activity in layer III was often followed within several milliseconds by negative field potentials in the terminal zones of the perforant path (stratum moleculare of the dentate gyrus and stratum lacunosum-moleculare of area CA1). The extracellular potentials recorded in the dentate gyrus corresponded to excitatory postsynaptic potentials and action potentials in dentate granule cells. However, extracellular potentials in area CA1 were small and rarely correlated with discharge in CA1 pyramidal cells. 6. The results demonstrate that AOAA application leads to an NMDA-receptor-dependent enhancement of evoked potentials in medial entorhinal cortical neurons, which appears to be irreversible. The potentials can be facilitated by repetitive stimulation, and lead to synchronized discharges of entorhinal neurons. The discharges invade other areas such as the hippocampus, indicating how seizure activity may spread after AOAA injection in vivo. These data suggest that AOAA may be a useful tool to study longlasting changes in NMDA receptor function that lead to epileptiform activity and neurodegeneration.