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bioRxiv · 10.1101/762450

MicroRNA-210 Knockout Alters Dendritic Density and Behavioural Flexibility

Watts, M.·Williams, G.·Lu, J.·Nithianantharajah, J.·Claudianos, C.
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Abstract

MicroRNAs exert post-transcriptional control over eukaryotic genomes and are integral for regulating complex functions in neurodevelopment, neuroplasticity and cognitive processing. The microRNA-210 (miR-210) is a highly-conserved, hypoxia-regulated miRNA that has been shown to be dysregulated in Alzheimers Disease. We have recently also identified a significant enrichment of neurodegenerative diseases among miR-210 targets within the human transcriptome. To further elucidate the role of miR-210 in neuronal function and cognitive behaviour, we utilised conditional miR-210 knockout mice to characterise miR-210 regulation and function in primary hippocampal neurons and measured visual discrimination and reversal learning using rodent touchscreen assays. We found that miR-210 expression was induced by neuronal activation and loss of neuronal miR-210 increased oxidative metabolism and ROS production as well as dendritic density and branching in vitro. We also found that loss of miR-210 in knockout mice increased behavioural flexibility and reduced perseverative responding during reversal learning which required updating of information and feedback. These data support a conserved, activity-dependent role for miR-210 in cognitive function through modulation of neuronal metabolism.

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Watts, M., Williams, G., Lu, J., Nithianantharajah, J., Claudianos, C.. 2019-09-08. MicroRNA-210 Knockout Alters Dendritic Density and Behavioural Flexibility. https://doi.org/10.1101/762450

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