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Synaptic Transmission Controls Radial Migration of Neurons
Science 20 Apr 2018: Vol. 360, Issue 6386, pp. 313-317 Synaptic transmission from subplate neurons controls radial migration of neocortical neurons Chiaki Ohtaka-Maruyama, et.al. Neural Network Project, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan. Center for Basic Technology Research, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan. Neural Development Project, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan. Anatomy and Cell Biology, Nagoya University Graduate School of Medicine, Aichi 466-8550, Japan. Department of Biology, Ochanomizu University, Tokyo 112-8610, Japan. Graduate School of Humanities and Sciences, Ochanomizu University, Tokyo 112-8610, Japan. School of Advanced Science and Engineering, Waseda University, Tokyo 169-0072, Japan. [paraphrase] The neocortex exhibits a six-layered structure that is formed by radial migration of excitatory neurons, for which the multipolar-to-bipolar transition of immature migrating multipolar neurons is required. Here, we report that subplate neurons, one of the first neuron types born in the neocortex, manage the multipolar-to-bipolar transition of migrating neurons. By histochemical, imaging, and microarray analyses on the mouse embryonic cortex, we found that subplate neurons extend neurites toward the ventricular side of the subplate and form transient glutamatergic synapses on the multipolar neurons just below the subplate. NMDAR (N-methyl-d-aspartate receptor)–mediated synaptic transmission from subplate neurons to multipolar neurons induces the multipolar-to-bipolar transition, leading to a change in migration mode from slow multipolar migration to faster radial glial-guided locomotion. Our data suggested that transient synapses formed on early immature neurons regulate radial migration. The six-layered neocortex develops through radial migration of excitatory neurons in an inside-out manner. Defects in this construction process lead to brain disorders such as lissencephaly. In the developing neocortex, excitatory neurons are generated from progenitors known as radial glial cells in the ventricular zone (VZ). Newly generated neurons exhibit a multipolar shape and meandering movement in the subventricular zone (SVZ) and intermediate zone (IZ) (multipolar migration). These multipolar neurons (MpNs) then change to a bipolar shape (multipolar-to-bipolar transition) and migrate rapidly in the cortical plate (CP) toward the marginal zone (MZ) via radial glial-guided locomotion (locomotion). Subplate neurons (SpNs) and Cajal-Retzius cells are the first neurons born in the neocortex and reside in the subplate (SP) and MZ, respectively. Cajal-Retzius cells guide the inside-out layering of excitatory neurons by secreting reelin. SpNs build connections between the thalamus and the cortex. Here, we examined the possibility that SpNs also regulate radial migration. Our data suggested that subplate neurons facilitate multipolar-to-bipolar transition of migrating excitatory neurons by NMDAR-mediated synaptic transmission, although the possibility that there are also contributions from deep layer neurons cannot be excluded. Impairment of multipolar-to-bipolar transition and accumulation of multipolar neurons below the subplate are observed in mice mutant for a variety of genes, including RP58; some of these genes are involved in human neurodevelopmental disorders such as fragile X syndrome. Subplate neurons might regulate the expression and function of these genes in multipolar neurons through NMDAR-mediated Ca2+ signaling. The subplate has been associated with autism and schizophrenia by gene expression profiling. Disruption of these transient synapses during development may contribute to these and other psychiatric disorders. [paraphrase]
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