Khalilov Ilgam, Le Van Quyen Michel, Gozlan Henri, Ben-Ari Yehezkel
INMED-INSERM, U 29 Marseille, 163, route de Luminy, 13273 Marseille Cedex 09, France.
Neuron. 2005 Dec 8;48(5):787-96. doi: 10.1016/j.neuron.2005.09.026.
GABA excites immature neurons and inhibits adult ones, but whether this contributes to seizures in the developing brain is not known. We now report that in the developing, but not the adult, hippocampus, seizures beget seizures only if GABAergic synapses are functional. In the immature hippocampus, seizures generated with functional GABAergic synapses include fast oscillations that are required to transform a naive network to an epileptic one: blocking GABA receptors prevents the long-lasting sequels of seizures. In contrast, in adult neurons, full blockade of GABA(A) receptors generates epileptogenic high-frequency seizures. Therefore, purely glutamatergic seizures are not epileptogenic in the developing hippocampus. We suggest that the density of glutamatergic synapses is not sufficient for epileptogenesis in immature neurons; excitatory GABAergic synapses are required for that purpose. We suggest that the synergistic actions of GABA and NMDA receptors trigger the cascades involved in epileptogenesis in the developing hippocampus.
γ-氨基丁酸（GABA）可使未成熟神经元兴奋，而使成熟神经元抑制，但这是否会导致发育中大脑的癫痫发作尚不清楚。我们现在报告，在发育中的而非成熟的海马体中，只有当GABA能突触发挥功能时，癫痫发作才会引发癫痫发作。在未成熟的海马体中，由功能性GABA能突触产生的癫痫发作包括快速振荡，这是将幼稚网络转变为癫痫网络所必需的：阻断GABA受体可防止癫痫发作的长期后果。相比之下，在成年神经元中，完全阻断GABAA受体会产生致痫性高频癫痫发作。因此，单纯的谷氨酸能癫痫发作在发育中的海马体中并不具有致痫性。我们认为，谷氨酸能突触的密度不足以在未成熟神经元中引发癫痫；为此需要兴奋性GABA能突触。我们认为，GABA和NMDA受体的协同作用触发了发育中海马体癫痫发生所涉及的级联反应。
