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Cilia-mediated cerebrospinal fluid flow modulates neuronal and astroglial activity in the zebrafish larval brain

ABSTRACT: The brain uses a specialized system to transport cerebrospinal fluid (CSF) that is essential for brain homeostasis. This system consists of interconnected ventricles lined by ependymal cells, which generate a directional flow upon beating of their motile cilia. Notably, motile cilia act jointly with other physiological factors, including active CSF secretion and cardiac pressure gradients, to regulate CSF dynamics. The content of CSF and its movement in brain ventricles are thought to be important for brain physiology. Yet, the link between cilia mediated CSF flow and brain function is poorly understood. In this study, we specifically addressed the role of motile cilia-mediated CSF flow on brain development and physiology using zebrafish larvae as a model system. By analyzing mutant animals with paralyzed cilia, we identified that loss of cilia motility did not alter progenitor proliferation, overall brain morphology, or baseline neural activity. Instead, we identified that loss of ciliary motility led to randomization of brain asymmetry. We also observed altered neuronal responses to photic stimulation, especially in the optic tectum and hindbrain. Since astroglia contact CSF at the ventricular walls and are essential for regulating neuronal activity, we next investigated astroglial activity in motile cilia mutants. Our analyses revealed a striking reduction in astroglial calcium signals both during spontaneous and light-evoked activity. Altogether, our findings highlight a novel role of motile cilia-mediated flow in regulating brain physiology through modulation of neural and astroglial networks.

ORGANISM(S): Danio rerio

PROVIDER: GSE254006 | GEO | 2024/11/22

REPOSITORIES: GEO

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