Long-term consequences of early postnatal seizures on hippocampal learning and plasticity
Long-term consequences of early postnatal seizures on hippocampal learning and plasticity
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DOI：
10.1046/j.1460-9568.2000.00117.x
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发表时间：
2000-07-01
影响因子：
3.4
通讯作者：
Sutula, T
中科院分区：
文献类型：
--
作者：
Lynch, M;Sayin, Ü;Sutula, T
神经活动影响突触连接的模式和发育中的感觉和运动系统的功能组织，但强烈的神经活动（如发育中的海马体中的癫痫发作）的长期后果尚未得到充分理解。为了评估早期发育期间异常神经活动可能对海马回路产生长期功能影响的可能性，海马回路在学习、记忆和癫痫中起作用，在出生后早期发育期间的特定日期，在经历了由红藻氨酸诱导的癫痫发作的成年大鼠中评估海马回路的功能特性。尽管先前的研究表明，与成年人相比，未成熟的海马对海人藻酸诱导的改变具有相对抵抗力，但独立的行为和生理实验表明，在出生后早期发育期间由海人藻酸诱发的癫痫发作诱导海马可塑性的长期丧失，表现为长时程增强能力降低，对点燃的敏感性降低，以及空间学习受损，这与齿状回中增强的成对脉冲抑制有关。当癫痫发作发生在出生后第一天时，抑制的增强和可塑性的丧失是最大的，但是当癫痫发作被诱导到出生后第14天时也观察到，这界定了发育中的大鼠海马体的出生后易感期，此时癫痫发作对正常神经活动的破坏对海马体产生一致的影响，依赖行为和几种形式的海马可塑性与成年期的学习、记忆和癫痫的发展有关。
Neural activity influences the patterning of synaptic connections and functional organization of developing sensory and motor systems, but the long-term consequences of intense neural activity such as seizures in the developing hippocampus are not adequately understood. To evaluate the possibility that abnormal neural activity during early development may have long-term functional effects in hippocampal circuitry that plays a role in learning, memory and epilepsy, functional properties of hippocampal circuitry were assessed in adult rats that had experienced seizures induced by kainic acid on specific days during early postnatal development. Although previous studies have suggested that the immature hippocampus is relatively resistant to seizure-induced alterations compared with adults, independent behavioural and physiological experiments demonstrated that seizures evoked by kainic acid during early postnatal development induced a long-term loss of hippocampal plasticity manifesting as reduced capacity for long-term potentiation, reduced susceptibility to kindling, and impaired spatial learning, which was associated with enhanced paired-pulse inhibition in the dentate gyrus. The enhancement of inhibition and loss of plasticity were maximal when the seizures occurred on the first day of life, but were also observed when seizures were induced as late as postnatal day 14, which delimited a period of postnatal susceptibility in the developing rat hippocampus when disruption of normal neural activity by seizures produced consistent effects on a hippocampal-dependent behaviour and several forms of hippocampal plasticity implicated in learning, memory and the development of epilepsy in adulthood.