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bioRxiv · 10.1101/2021.05.12.443573

microRNA-138 controls hippocampal interneuron function and short-term memory

Schratt, G.·Daswani, R.·Gilardi, C.·Soutschek, M.·Weiss, K.·Bicker, S.·Fiore, R.·Dieterich, C.·Germain, P.-L.·Winterer, J.
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Abstract

The proper development and function of neuronal circuits relies on a tightly regulated balance between excitatory and inhibitory (E/I) synaptic transmission, and disrupting this balance can cause neurodevelopmental disorders, e.g. schizophrenia. microRNA-dependent gene regulation in pyramidal neurons is important for excitatory synaptic function and cognition, but its role in inhibitory interneurons is poorly understood. Here, we identify miR-138-5p as a regulator of short-term memory and inhibitory synaptic transmission in the hippocampus. Sponge-mediated miR-138-5p inactivation specifically in parvalbumin (PV)-expressing interneurons impairs spatial recognition memory and enhances GABAergic synaptic input onto pyramidal neurons. Cellular and behavioural phenotypes associated with miR-138-5p inactivation are paralleled by an upregulation of the schizophrenia-associated Erbb4, which we validated as a direct miR-138-5p target gene. Our findings suggest that miR-138-5p is a critical regulator of PV interneuron function, with implications for cognition and schizophrenia. More generally, they provide evidence that microRNAs orchestrate neural circuit development by fine-tuning both excitatory and inhibitory synaptic transmission.

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Schratt, G., Daswani, R., Gilardi, C., Soutschek, M., Weiss, K., Bicker, S., Fiore, R., Dieterich, C., Germain, P.-L., Winterer, J.. 2021-05-13. microRNA-138 controls hippocampal interneuron function and short-term memory. https://doi.org/10.1101/2021.05.12.443573

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