Characterization of the circuits that generate spontaneous episodes of activity in the early embryonic mouse spinal cord
Characterization of the circuits that generate spontaneous episodes of activity in the early embryonic mouse spinal cord
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DOI：
10.1523/jneurosci.23-02-00587.2003
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发表时间：
2003-01-15
影响因子：
5.3
通讯作者：
Landmesser, LT
中科院分区：
文献类型：
--
作者：
Hanson, MG;Landmesser, LT
在发育中的神经系统中，有模式的自发活动影响多种发育过程。因此，确定这种活动最早发生的时间和表征底层电路是很重要的。在离体小鼠脊髓肢体制备中，早在胚胎第11天(E11)-E12天就出现了高节律性自发活动，当时许多腰骶运动神经元仍在迁移并扩展其外周投射。这种活动需要电和化学传递，而乙酰胆碱，而不是谷氨酸，提供主要的兴奋驱动。我们的数据与运动神经元本身通过二氢- β -红血碱-不敏感的烟碱受体在彼此之间和gaba能中间神经元上建立兴奋性连接，在产生这种活动中起关键作用是一致的。这导致了局部爆发的产生。与这些观察结果一致，观察到HRP逆行标记的E12-E12.5小鼠运动神经元具有广泛的轴突侧枝，局部投射到外侧运动柱内，并投射到外侧运动柱背侧和内侧含有中间神经元的区域。胆碱能轴突，可能来自运动神经元，也被观察到在腹侧和外侧的输尿管。然而，局部爆发在脊髓中传播，需要另一条dhβ敏感的胆碱能通路，也涉及甘氨酸能中间神经元。这种神经回路特征应该有助于利用改变中间神经元特定亚群或胆碱能传递的基因突变来确定改变这种早期活动的不同方面如何影响脊髓运动回路的后续发育。
In the developing nervous system, patterned spontaneous activity affects a variety of developmental processes. Thus, it is important to identify the earliest time that such activity occurs and to characterize the underlying circuitry. In isolated mouse spinal cord-limb preparations, highly rhythmic spontaneous activity occurred as early as embryonic day 11 (E11)-E12, when many lumbosacral motoneurons were still migrating and extending their peripheral projections. This activity required both electrical and chemical transmission, and acetylcholine, rather than glutamate, provided the main excitatory drive. Our data are consistent with motoneurons themselves playing a critical role in generating such activity by making excitatory connections on each other and on GABAergic interneurons via dihydro-beta-erythroidine hydrobromide (DHbetaE)-insensitive nicotinic receptors. This resulted in the generation of local bursts. Consistent with these observations, E12-E12.5 mouse motoneurons retrogradely labeled by HRP were observed to have extensive axon collaterals that projected locally within the lateral motor column and to interneuron-containing regions dorsal and medial of the lateral motor column. Cholinergic axons, presumably from motoneurons, were also observed in the ventral and lateral funiculi. However, for local bursts to propagate throughout the cord, a second DHbetaE-sensitive cholinergic pathway that also involved glycinergic interneurons was required. This circuit characterization should facilitate the use of genetic mutations that alter specific subpopulations of interneurons or cholinergic transmission to determine how modifying different aspects of this early activity affects subsequent development of the spinal motor circuit.