MicroRNA-210 Regulates Dendritic Morphology and Behavioural Flexibility in Mice

MicroRNAs are known to be critical regulators of neuronal plasticity. The highly conserved, hypoxia-regulated microRNA-210 (miR-210) has been shown to be associated with long-term memory in invertebrates and dysregulated in neurodevelopmental and neurodegenerative disease models. However, the role of miR-210 in mammalian neuronal function and cognitive behaviour remains unexplored. Here we generated Nestin-cre-driven miR-210 neuronal knockout mice to characterise miR-210 regulation and function using in vitro and in vivo methods. We identified miR-210 localisation throughout neuronal somas and dendritic processes and increased levels of mature miR-210 in response to neural activity in vitro. Loss of miR-210 in neurons resulted in higher oxidative phosphorylation and ROS production following hypoxia and increased dendritic arbour density in hippocampal cultures. Additionally, miR-210 knockout mice displayed altered behavioural flexibility in rodent touchscreen tests, particularly during early reversal learning suggesting processes underlying updating of information and feedback were impacted. Our findings support a conserved, activity-dependent role for miR-210 in neuroplasticity and cognitive function.