Lynch M, Sayin U, Bownds J, Janumpalli S, Sutula T
Department of Neurology, University of Wisconsin, H6/574 Clinical Sciences Center, Madison 53792, USA.
Eur J Neurosci. 2000 Jul;12(7):2252-64. doi: 10.1046/j.1460-9568.2000.00117.x.
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.
神经活动会影响突触连接的模式以及发育中的感觉和运动系统的功能组织，但对于发育中的海马体中强烈神经活动（如癫痫发作）的长期后果，我们尚未有充分的了解。为了评估早期发育过程中异常神经活动可能对在学习、记忆和癫痫中起作用的海马体回路产生长期功能影响的可能性，我们对在出生后早期特定天数经历过由 kainic 酸诱导癫痫发作的成年大鼠的海马体回路功能特性进行了评估。尽管先前的研究表明，与成年海马体相比，未成熟的海马体对癫痫发作引起的改变具有相对抗性，但独立的行为学和生理学实验表明，出生后早期发育期间由 kainic 酸诱发的癫痫发作会导致海马体可塑性的长期丧失，表现为长期增强能力降低、对点燃的易感性降低以及空间学习受损，这与齿状回中配对脉冲抑制的增强有关。当癫痫发作发生在出生第一天时，抑制增强和可塑性丧失最为明显，但在出生后第 14 天诱发癫痫发作时也观察到了这种情况，这界定了发育中大鼠海马体的出生后易感性时期，在此期间癫痫发作对正常神经活动的破坏会对海马体依赖行为以及与成年期学习、记忆和癫痫发展相关的几种海马体可塑性形式产生一致影响。
