microRNA-138 controls hippocampal interneuron function and short-term memory in mice
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 miR138-5p as a regulator of short-term memory and inhibitory synaptic transmission in the mouse hippocampus. Sponge-mediated miR138-5p inactivation specifically in mouse parvalbumin (PV)-expressing interneurons impairs spatial recognition memory and enhances GABAergic synaptic input onto pyramidal neurons. Cellular and behavioural phenotypes associated with miR138-5p inactivation are paralleled by an upregulation of the schizophrenia-associated Erbb4, which we validated as a direct miR138-5p target gene. Our findings suggest that miR138-5p is a critical regulator of PV interneuron function in mice, 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.
RNA-seq data has been deposited to GEO (accession no. GSE173982
miR-138 controls interneuron function and short-term memoryNCBI Gene Expression Omnibus, GSE173982.
Article and author information
Deutsche Forschungsgemeinschaft (SCHR 1136/4-2)
- Gerhard Schratt
Eidgenössische Technische Hochschule Zürich (24 18-2 (NeuroSno))
- Gerhard Schratt
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Animal experimentation: All procedures were conducted in strict accordance with the National Institutes of Health Guidelines for the Care and Use of Laboratory Animals and the relevant local or national rules and regulations of Switzerland and were subject to prior authorization by the local cantonal authorities (ZH017/2018, ZH196/17).
- John R Huguenard, Stanford University School of Medicine, United States
- Preprint posted: May 13, 2021 (view preprint)
- Received: September 20, 2021
- Accepted: March 13, 2022
- Accepted Manuscript published: March 15, 2022 (version 1)
- Version of Record published: March 29, 2022 (version 2)
© 2022, Daswani et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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