Pharmacological mechanisms underlying switching from the large-scale depolarization wave to segregated activity in...

During the early development of the nervous system, synchronized activity is observed in a variety of structures, and is considered to play a fundamental role in neural development. One of the most striking examples of such activity is the depolarization wave reported in chick and rat embryos. In the accompanying paper (Momose-Sato et al., 2012), we have demonstrated that a depolarization wave is also present in the mouse embryo by showing large-scale optical waves, which spread remarkably over the central nervous system, including the spinal cord, hindbrain, cerebellum, midbrain, and forebrain. In the present study, we examined the pharmacological nature of the mouse depolarization wave and its developmental changes. We show here that two types of switching in pharmacological characteristics occur during development. One is that the depolarization wave is strongly dependent on nicotinic acetylcholine receptors during the early developmental stage [embryonic day (E)11-12], but is dominated by glutamate at the later stage (E13 onwards). The second is that γ-aminobutyric acid (GABA), which acts as an excitatory mediator of the depolarization wave during the early phase, becomes an inhibitory modulator by E14. These changes seemed to occur earlier in the hindbrain than in the spinal cord. Furthermore, we show that the second switch causes the loss of synchronization over the network, resulting in the disappearance of the depolarization wave and segregation of the activity into discrete regions of the medulla and spinal cord. We suggest that pharmacological switching is a possible mechanism underlying replacement of the primordial correlated network by a mature neuronal circuit.