Chronic changes in synaptic responses of entorhinal and hippocampal neurons after amino-oxyacetic acid (AOAA)-induced entorhinal cortical neuron loss.
Chronic changes in synaptic responses of entorhinal and hippocampal neurons after amino-oxyacetic acid (AOAA)-induced entorhinal cortical neuron loss.
复制标题
氨基氧乙酸（AOAA）诱导内嗅皮质神经元丢失后，内嗅和海马神经元突触反应的慢性变化。
DOI：
10.1152/jn.1998.80.6.3031
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发表时间：
1998
期刊：
影响因子：
--
通讯作者：
Schwarcz,R
中科院分区：
文献类型：
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作者：
Scharfman,HE;Goodman,JH;Du,F;Schwarcz,R
E.，J. H.Goodman，F.Du，and R.Schwarcz.内嗅神经元和海马神经元在氨基氧乙酸诱导的内嗅神经元丢失后突触反应的时间变化.神经生理学杂志，80：3031-3046,1998.用氨基氧乙酸局灶性注射(AOAA)造成单侧内嗅觉损伤后1个月至1.5年，在体内和体外观察内嗅皮层和海马神经元的突触反应。已有研究表明，将AOAA注射到内侧内嗅皮质，优先导致第三层细胞丢失。虽然行为发作在∼治疗后2小时停止，但在1.5年后在内嗅皮层和海马区仍可记录到异常诱发反应。在AOAA处理大鼠的大部分脑片中，内侧内嗅觉皮质浅层记录到的对白质、小脑前或小结旁刺激的反应是异常的。细胞外记录的对白质刺激的反应在浅层延长且重复。细胞内记录显示，与短暂的兴奋性突触后电位(EPSPS)和单次放电相比，对照组浅层残余主细胞产生长时间重复的兴奋性突触后电位(EPSPS)和放电。AOAA处理组大鼠深层神经元的初始突触反应与对照组无差异。然而，在其中一些神经元中，在延迟之后出现了额外的兴奋性活动期。在病变半球的同侧和对侧脑片上记录到异常反应。活体内嗅皮层的记录也异常，刺激CA1区/丘脑下部交界区的延长和重复反应证明了这一点。在体外或体内记录的海马神经元的诱发反应，在选定的通路中显示出异常，例如体外CA3神经元对肺门刺激的反应。在AOAA处理的大鼠中，CA1群峰电位对重复的CA3刺激反应的增强持续时间不足。AOAA处理组大鼠CA1区和齿状回的Theta活动幅度降低，但对角束刺激的诱发反应不能与对照组区分。结果表明，优先损毁内嗅皮层的第三层可使部分内嗅皮层和海马区的诱发和自发活动发生持久的改变。由于AOAA引起的损害与颞叶癫痫患者的内嗅觉损害相似，这些数据支持这样的假设，即优先损害内嗅觉皮质有助于兴奋性的长期变化，这可能与颞叶癫痫的病因有关。
Scharfman, H. E., J. H. Goodman, F. Du, and R. Schwarcz.Chronic changes in synaptic responses of entorhinal and hippocampal neurons after amino-oxyacetic acid (AOAA)–induced entorhinal neuron loss.J. Neurophysiol.80: 3031–3046, 1998. Synaptic responses of entorhinal cortical and hippocampal neurons were examined in vivo and in vitro, 1 mo to 1.5 yr after a unilateral entorhinal lesion caused by a focal injection of amino-oxyacetic acid (AOAA). It has been shown previously that injection of AOAA into the medial entorhinal cortex produces cell loss in layer III preferentially. Although behavioral seizures stopped ∼2 h after AOAA treatment, abnormal evoked responses were recorded as long as 1.5 yr later in the entorhinal cortex and hippocampus. In the majority of slices from AOAA-treated rats, responses recorded in the superficial layers of the medial entorhinal cortex to white matter, presubiculum, or parasubiculum stimulation were abnormal. Extracellularly recorded responses to white matter stimulation were prolonged and repetitive in the superficial layers. Intracellular recordings showed that residual principal cells in superficial layers produced prolonged, repetitive excitatory postsynaptic potentials (EPSPs) and discharges in response to white matter stimulation compared with brief EPSPs and a single discharge in controls. Responses of deep layer neurons of AOAA-treated rats did not differ from controls in their initial synaptic response. However, in a some of these neurons, additional periods of excitatory activity occurred after a delay. Abnormal responses were recorded from slices ipsilateral as well as contralateral to the lesioned hemisphere. Recordings from the entorhinal cortex in vivo were abnormal also, as demonstrated by prolonged and repetitive responses to stimulation of the area CA1/subiculum border. Evoked responses of hippocampal neurons, recorded in vitro or in vivo, demonstrated abnormalities in selected pathways, such as responses of CA3 neurons to hilar stimulation in vitro. There was a deficit in the duration of potentiation of CA1 population spikes in response to repetitive CA3 stimulation in AOAA-treated rats. Theta activity was reduced in amplitude in area CA1 and the dentate gyrus of AOAA-treated rats, although evoked responses to angular bundle stimulation could not be distinguished from controls. The results demonstrate that a preferential lesion of layer III of the entorhinal cortex produces a long-lasting change in evoked and spontaneous activity in parts of the entorhinal cortex and hippocampus. Given the similarity of the lesion produced by AOAA and entorhinal lesions in temporal lobe epileptics, these data support the hypothesis that preferential damage to the entorhinal cortex contributes to long-lasting changes in excitability, which could be relevant to the etiology of temporal lobe epilepsy.