Calcium Signaling in the Cerebellar Radial Glia and Its Association with Morphological Changes during Zebrafish Development.

Elizabeth Pereida-Jaramillo,Angeles Edith Espino-Saldaña,Gabriela B Gómez-González,Ataúlfo Martínez-Torres

doi:10.3390/ijms222413509

Elizabeth Pereida-Jaramillo, Angeles Edith Espino-Saldaña + Show 2 more

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https://doi.org/10.3390/ijms222413509

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Abstract

Radial glial cells are a distinct non-neuronal cell type that, during development, span the entire width of the brain walls of the ventricular system. They play a central role in the origin and placement of neurons, since their processes form structural scaffolds that guide and facilitate neuronal migration. Furthermore, glutamatergic signaling in the radial glia of the adult cerebellum (i.e., Bergmann glia), is crucial for precise motor coordination. Radial glial cells exhibit spontaneous calcium activity and functional coupling spread calcium waves. However, the origin of calcium activity in relation to the ontogeny of cerebellar radial glia has not been widely explored, and many questions remain unanswered regarding the role of radial glia in brain development in health and disease. In this study we used a combination of whole mount immunofluorescence and calcium imaging in transgenic (gfap-GCaMP6s) zebrafish to determine how development of calcium activity is related to morphological changes of the cerebellum. We found that the morphological changes in cerebellar radial glia are quite dynamic; the cells are remarkably larger and more elaborate in their soma size, process length and numbers after 7 days post fertilization. Spontaneous calcium events were scarce during the first 3 days of development and calcium waves appeared on day 5, which is associated with the onset of more complex morphologies of radial glia. Blockage of gap junction coupling inhibited the propagation of calcium waves, but not basal local calcium activity. This work establishes crucial clues in radial glia organization, morphology and calcium signaling during development and provides insight into its role in complex behavioral paradigms.

Highlights

The cerebellum is involved in sensorimotor processing function, and recent evidence suggests its role in cognition and emotion [1,2]
The results showed that cerebellar radial glia display spontaneous calcium elevations even before neuronal circuit formation, and higher calcium activity coincided with an increase in radial glia morphological complexity
To monitor the morphological changes of cerebellar radial glia during zebrafish development, we focused on larvae at 3, 5 and 7 dpf

Summary

Introduction

The cerebellum is involved in sensorimotor processing function, and recent evidence suggests its role in cognition and emotion [1,2]. Considering all the clinical implications of cerebellar function and that its defects can induce motor and other neurological conditions by interacting with diverse brain areas, there is emerging interest in studying the development and functional organization of the cerebellum. The overall organization and cell types of the cerebellum are highly conserved from fish to mammals [6,7,8]. Radial glia cells are evolutionarily conserved embryonic neural stem cells that, in the adult cerebellum, remain as Bergmann glia [9,10]. Radial glia cells are transformed into multiciliate ependymal cells, and in adult fish they remain as neural stem cells [12,13]

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