Molecular Neurobiology Laboratory, The Salk Institute, La Jolla, California 92037, USA.
J Neurosci. 2012 Apr 4;32(14):4755-61. doi: 10.1523/JNEUROSCI.6412-11.2012.
Approximately one in five neurons is GABAergic in many neocortical areas and species, forming a critical balance between inhibition and excitation in adult circuits. During development, cortical GABAergic neurons are generated in ventral telencephalon and migrate up to developing cortex where the excitatory glutamatergic neurons are born. We ask here: when during development is the adult GABAergic/glutamatergic neuron ratio first established? To answer this question, we have determined the fraction of all neocortical GABAergic neurons that will become inhibitory (GAD67(+)) in mice from embryonic day 10.5 (E10.5) to postnatal day 28 (P28). We find that this fraction is close to 1/5, the adult value, starting from early in corticogenesis (E14.5, when GAD67(+) neurons are still migrating tangentially to the cortex) and continuing at the same 1/5 value throughout the remainder of brain development. Thus our data indicate the one-in-five fraction of GABAergic neurons is already established during their neuronal migration and well before significant synapse formation.
在许多新皮层区域和物种中,大约五分之一的神经元是 GABA 能的,在成年回路中形成抑制和兴奋之间的关键平衡。在发育过程中,皮质 GABA 能神经元在前脑腹侧产生,并迁移到兴奋性谷氨酸能神经元产生的发育中的皮质。我们在这里提出:在发育过程中,成年 GABA 能/谷氨酸能神经元的比例最早是在什么时候建立的?为了回答这个问题,我们已经确定了从胚胎第 10.5 天(E10.5)到出生后第 28 天(P28)的小鼠所有新皮层 GABA 能神经元中有多少将成为抑制性的(GAD67(+))。我们发现,从皮质发生早期(E14.5,此时 GAD67(+)神经元仍沿切线迁移到皮质)开始,这个分数接近 1/5,即成年值,并在大脑发育的其余部分以相同的 1/5 值继续。因此,我们的数据表明,在神经元迁移过程中,五分之一的 GABA 能神经元比例已经建立,并且远早于显著的突触形成之前。