Development of an L-type Ca2+ channel-dependent Ca2+ transient during the radial migration of cortical excitatory neurons

Abstract

Increasing evidence has shown that voltage-gated L-type Ca²⁺ channels (LTCCs) are crucial for neurodevelopmental events, including neuronal differentiation/migration and neurite morphogenesis/extension. However, the time course of their functional maturation during the development of excitatory neurons remains unknown. Using a combination of fluorescence in situ hybridization and in utero electroporation-based labeling, we found that the transcripts of Cacna1c and Cacna1d, which encode the LTCC pore-forming subunits, were upregulated in the intermediate zone (IZ) during radial migration. Ca²⁺ imaging using GCaMP6s in acute brain slices showed spontaneous Ca²⁺ transients in migrating neurons throughout the IZ. Neurons in the IZ upper layer, especially in the multipolar-to-bipolar transition layer (TL), exhibited more frequent Ca²⁺ transients than adjacent layers and responded to FPL64176, a potent activator of LTCC. Consistently, nimodipine, an LTCC blocker, inhibited spontaneous Ca²⁺ transients in neurons in the TL. Collectively, we showed a hitherto unknown increased prevalence of LTCC-dependent Ca²⁺ transients in the TL of the IZ upper layer during the radial migration of excitatory neurons, which could be essential for the regulation of Ca²⁺-dependent neurodevelopmental processes.

Keywords: Ca(2+) transients; Cacna1c; Cacna1d; GCaMP; Intermediate zone; Migrating neurons; Neurodevelopment; Voltage-gated L-type Ca(2+) channel (LTCC).