Optical analysis of functional formation of the brainstem neural circuit and its r egulation by the depolarization wave

在发育中的中枢神经系统（CNS）中，未成熟的神经网络在大范围内产生自发的相关活动。利用电压敏感染料的光学成像技术，我们在大鼠和鸡胚胎中发现了一种广泛传播的波，称为去极化波。去极化波的一个新奇之处在于它在中枢神经系统的广泛区域传播，包括脑干、脊髓、小脑和大脑的一部分。另一个突出的特征是，它是由各种类型的感觉输入和内源性自发活动非特异性触发的。这些资料表明，脑电波可能不是一个简单的特定神经元回路形成的调节器，但可能在中枢神经系统的发展中发挥更广泛的作用。去极化波由多种神经递质和间隙连接介导，随着发育，优势递质由乙酰胆碱转向谷氨酸。对去极化波起源的监测显示，去极化波最初起源于上颈髓/下髓质，在后期由多个区域产生。该网络可能是维持发育中的中枢神经系统相关活动的自分配系统。

In the developing central nervous system (CNS), immature neural networks generate spontaneous correlated activity in a wide range. Using the optical imaging technique with voltage-sensitive dyes, we found a widely-spreading wave in the rat and chick embryos, which was termed the depolarization wave. One novelty of the depolarization wave was that it traveled over a wide region of the CNS including the brainstem, spinal cord, cerebellum, and part of the cerebrum. Another outstanding feature was that it was non-specifically triggered by various types of sensory inputs as well as endogenous spontaneous activity. These profiles suggest that the wave may not serve as a simple regulator of specific neuronal circuit formation, but might play a more global role in CNS development. The depolarization wave was mediated by multiple neurotransmitters and gap junctions, and the dominant transmitter switched from acetylcholine to glutamate with development. Surveillance of the origin of the depolarization wave showed that the wave initially originated in the upper cervical cord/lower medulla near the obex and was generated by multiple regions at the later stages. This network possibly works as a self-distribution system that maintains the correlated activity in the developing CNS.