斎藤 哲一郎

In developing brains, activity-dependent remodeling facilitates the formation of precise neuronal connectivity. Synaptic competition is known to facilitate synapse elimination; however, it has remained unknown how different synapses compete with one another within a post-synaptic cell. Here, we investigate how a mitral cell in the mouse olfactory bulb prunes all but one primary dendrite during the developmental remodeling process. We find that spontaneous activity generated within the olfactory bulb is essential. We show that strong glutamatergic inputs to one dendrite trigger branch-specific changes in RhoA activity to facilitate the pruning of the remaining dendrites: NMDAR-dependent local signals suppress RhoA to protect it from pruning; however, the subsequent neuronal depolarization induces neuron-wide activation of RhoA to prune non-protected dendrites. NMDAR-RhoA signals are also essential for the synaptic competition in the mouse barrel cortex. Our results demonstrate a general principle whereby activity-dependent lateral inhibition across synapses establishes a discrete receptive field of a neuron.

Abstract mRNA vaccines for SARS-CoV-2 have been widely used and saving millions of people in the world. How efficiently proteins are produced from exogenous mRNAs in the embryonic brain, however, is less known. Here we show that protein expression occurs highly efficiently in neural stem cells, in a very narrow time window after mRNA electroporation in the embryonic mouse brain, where plasmids have been successfully transfected. Protein expression is detected 1 h and 12 h after the electroporation of mRNAs and plasmids, respectively. The delivery of exogenous mRNAs may be useful for not only vaccines but also functional analysis in the brain.

Schizophrenia is a devastating neuropsychiatric disease with a globally 1% life-long prevalence. Clinical studies have linked <italic>Zswim6</italic> mutations to developmental and neurological diseases, including schizophrenia. <italic>Zswim6</italic>’s function remains largely unknown. Given the involvement of <italic>Zswim6</italic> in schizophrenia and schizophrenia as a neurodevelopmental disease, it is important to understand the spatiotemporal expression pattern of <italic>Zswim6</italic> in the developing brain. Here, we performed a comprehensive analysis of the spatiotemporal expression pattern of <italic>Zswim6</italic> in the mouse forebrain by <italic>in situ</italic> hybridization with radioactive and non-radioactive-labeled riboprobes. <italic>Zswim6</italic> mRNA was detected as early as E11.5 in the ventral forebrain. At E11.5–E13.5, <italic>Zswim6</italic> was highly expressed in the lateral ganglionic eminence (LGE). The LGE consisted of two progenitor populations. Dlx⁺;Er81⁺ cells in dorsal LGE comprised progenitors of olfactory bulb interneurons, whereas Dlx⁺;Isl1⁺ progenitors in ventral LGE gave rise to striatal projection neurons. <italic>Zswim6</italic> was not colocalized with Er81 in the dorsal LGE. In the ventral LGE, <italic>Zswim6</italic> was colocalized with striatal progenitor marker <italic>Nolz-1</italic>. <italic>Zswim6</italic> was highly expressed in the subventricular zone (SVZ) of LGE in which progenitors undergo the transition from proliferation to differentiation. Double labeling showed that <italic>Zswim6</italic> was not colocalized with proliferation marker Ki67 but was colocalized with differentiation marker Tuj1 in the SVZ, suggesting <italic>Zswim6</italic> expression in early differentiating neurons. <italic>Zswim6</italic> was also expressed in the adjacent structures of medial and caudal ganglionic eminences (MGE, CGE) that contained progenitors of cortical interneurons. At E15.5 and E17.5, <italic>Zswim6</italic> was expressed in several key brain regions that were involved in the pathogenesis of schizophrenia, including the striatum, cerebral cortex, hippocampus, and medial habenular nucleus. <italic>Zswim6</italic> was persistently expressed in the postnatal brain. Cell type analysis indicated that <italic>Zswim6</italic> mRNA was colocalized with <italic>D1R</italic>-expressing striatonigral and <italic>D2R</italic>-expressing striatopallidal neurons of the adult striatum with a higher colocalization in striatopallidal neurons. These findings are of particular interest as striatal dopamine D2 receptors are known to be involved in the pathophysiology of schizophrenia. In summary, the comprehensive analysis provides an anatomical framework for the study of <italic>Zswim6 function and Zswim6-associated neurological disorders</italic>.