B&A Therapeutics, Marseille 13009, France
Neurochlore, Marseille 13009, France.
eNeuro. 2024 May 29;11(5). doi: 10.1523/ENEURO.0538-23.2024. Print 2024 May.
Cholinergic neurons of the basal forebrain represent the main source of cholinergic innervation of large parts of the neocortex and are involved in adults in the modulation of attention, memory, and arousal. During the first postnatal days, they play a crucial role in the development of cortical neurons and cortical cytoarchitecture. However, their characteristics, during this period have not been studied. To understand how they can fulfill this role, we investigated the morphological and electrophysiological maturation of cholinergic neurons of the substantia innominata-nucleus basalis of Meynert (SI/NBM) complex in the perinatal period in mice. We show that cholinergic neurons, whether or not they express gamma-aminobutyric acid (GABA) as a cotransmitter, are already functional at Embryonic Day 18. Until the end of the first postnatal week, they constitute a single population of neurons with a well developed dendritic tree, a spontaneous activity including bursting periods, and a short-latency response to depolarizations (early-firing). They are excited by both their GABAergic and glutamatergic afferents. During the second postnatal week, a second, less excitable, neuronal population emerges, with a longer delay response to depolarizations (late-firing), together with the hyperpolarizing action of GABA receptor-mediated currents. This classification into early-firing (40%) and late-firing (60%) neurons is again independent of the coexpression of GABAergic markers. These results strongly suggest that during the first postnatal week, the specific properties of developing SI/NBM cholinergic neurons allow them to spontaneously release acetylcholine (ACh), or ACh and GABA, into the developing cortex.
基底前脑的胆碱能神经元是大脑皮层大部分区域胆碱能神经支配的主要来源，在成人中参与注意力、记忆和觉醒的调节。在出生后的头几天，它们在皮质神经元和皮质细胞结构的发育中起着至关重要的作用。然而，在这一时期，它们的特征尚未得到研究。为了了解它们如何发挥这一作用，我们研究了围产期小鼠脑桥基底核复合体（Meynert）的脑桥基底核复合体（substantia innominata-nucleus basalis of Meynert，SI/NBM）胆碱能神经元的形态和电生理成熟。我们发现，无论是否表达γ-氨基丁酸（GABA）作为共递质，胆碱能神经元在胚胎第 18 天就已经具有功能。直到第一周结束，它们构成了一个具有发达树突的神经元群体，具有自发活动，包括爆发期，以及对去极化的短潜伏期反应（早期放电）。它们被 GABA 能和谷氨酸能传入所兴奋。在第二周，出现了第二个兴奋性较低的神经元群体，其对去极化的延迟反应较长（晚期放电），同时伴有 GABA 受体介导的电流的超极化作用。这种将神经元分为早期放电（40%）和晚期放电（60%）的分类方法再次与 GABA 能标记物的共表达无关。这些结果强烈表明，在出生后的第一周，发育中的 SI/NBM 胆碱能神经元的特定特性使它们能够自发地将乙酰胆碱（ACh）或 ACh 和 GABA 释放到发育中的皮质中。
