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Key points • A wave of electrical activity occurs in the developing brain for a certain period of time before sensory, motor and cognitive functions mature. • This electrical activity, or spontaneous activity, originates, spreads, then later retracts and disappears in specific areas of the brain at specific time points, but how it retracts is unknown. • We report that retraction in the mouse embryonic hindbrain is caused by a reduced excitability in the network of cells. This process can be reversed by bath application of high K+ solution, which increases excitability. • This reduced excitability is probably caused by increased number of K+ pores that are always open in individual cells. • These results help us understand how the spread of spontaneous activity is regulated and ultimately help us better understand the role of electrical activity during development of the fetal brain. Abstract Spontaneous activity supports developmental processes in many brain regions during embryogenesis, and the spatial extent and frequency of the spontaneous activity are tightly regulated by stage. In the developing mouse hindbrain, spontaneous activity propagates widely and the waves can cover the entire hindbrain at E11.5. The activity then retracts to waves that are spatially restricted to the rostral midline at E13.5, before disappearing altogether by E15.5. However, the mechanism of retraction is unknown. We studied passive membrane properties of cells that are spatiotemporally relevant to the pattern of retraction in mouse embryonic hindbrain using whole-cell patch clamp and imaging techniques. We find that membrane excitability progressively decreases due to hyperpolarization of resting membrane potential and increased resting conductance density between E11.5 and E15.5, in a spatiotemporal pattern correlated with the retraction sequence. Retraction can be acutely reversed by membrane depolarization at E15.5, and the induced events propagate similarly to spontaneous activity at earlier stages, though without involving gap junctional coupling. Manipulation of [K+]o or [Cl−]o reveals that membrane potential follows EK more closely than ECl, suggesting a dominant role for K+ conductance in the membrane hyperpolarization. Reducing membrane excitability by hyperpolarization of the resting membrane potential and increasing resting conductance are effective mechanisms to desynchronize spontaneous activity in a spatiotemporal manner, while allowing information processing to occur at the synaptic and cellular level. |
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