Gaiarsa J L, McLean H, Congar P, Leinekugel X, Khazipov R, Tseeb V, Ben-Ari Y
Institut National de la Santé et de la Recherche Médicale, U29, Hôpital de Port-Royal, Paris, France.
J Neurobiol. 1995 Mar;26(3):339-49. doi: 10.1002/neu.480260306.
In the adult central nervous system, GABAergic synaptic inhibition is known to play a crucial role in preventing the spread of excitatory glutamatergic activity. This inhibition is achieved by a membrane hyperpolarization through the activation of postsynaptic gamma-aminobutyric acidA (GABAA) and GABAB receptors. In addition, GABA also depress transmitter release acting through presynaptic GABAB receptors. Despite the wealth of data regarding the role of GABA in regulating the degree of synchronous activity in the adult, little is known about GABA transmission during early stages of development. In the following we report that GABA mediates most of the excitatory drive at early stages of development in the hippocampal CA3 region. Activation of GABAA receptors induces a depolarization and excitation of immature CA3 pyramidal neurons and increases intracellular Ca2+ ([Ca2+]i)] during the first postnatal week of life. During the same developmental period, the postsynaptic GABAB-mediated inhibition is poorly developed. In contrast, the presynaptic GABAB-mediated inhibition is well developed at birth and plays a crucial role in modulating the postsynaptic activity by depressing transmitter release at early postnatal stages. We have also shown that GABA plays a trophic role in the neuritic outgrowth of cultured hippocampal neurons.
在成体中枢神经系统中，已知γ-氨基丁酸（GABA）能突触抑制在防止兴奋性谷氨酸能活动扩散方面发挥关键作用。这种抑制是通过激活突触后γ-氨基丁酸A（GABAA）和GABAB受体使膜超极化来实现的。此外，GABA还通过作用于突触前GABAB受体抑制神经递质释放。尽管关于GABA在调节成体同步活动程度方面作用的数据丰富，但对于发育早期阶段的GABA传递却知之甚少。在下文中，我们报告GABA在海马CA3区发育早期介导了大部分兴奋性驱动。在出生后的第一周内，GABAA受体的激活会诱导未成熟CA3锥体神经元去极化并兴奋，并增加细胞内钙离子浓度（[Ca2+]i）。在同一发育时期，突触后GABAB介导的抑制作用发育不完善。相反，突触前GABAB介导的抑制在出生时就已充分发育，并在出生后早期通过抑制神经递质释放来调节突触后活动方面发挥关键作用。我们还表明，GABA在培养的海马神经元的神经突生长中发挥营养作用。
