MicroRNA-138 controls hippocampal interneuron function and short-term memory in mice
Abstract
The proper development and function of neuronal circuits rely on a tightly regulated balance between excitatory and inhibitory (E/I) synaptic transmission, and disrupting this balance can cause neurodevelopmental disorders, for example, 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 behavioral phenotypes associated with miR138-5p inactivation are paralleled by an upregulation of the schizophrenia (SCZ)-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 SCZ. More generally, they provide evidence that microRNAs orchestrate neural circuit development by fine-tuning both excitatory and inhibitory synaptic transmission. Show more
Permanent link
https://doi.org/10.3929/ethz-b-000541835Publication status
publishedExternal links
Journal / series
eLifeVolume
Pages / Article No.
Publisher
eLife Sciences PublicationsOrganisational unit
09498 - Schratt, Gerhard / Schratt, Gerhard
Funding
ETH-24 18-2 - The contribution of snoRNA function to the control of neuroplasticity in the context of affective disorders (NeuroSno) (ETHZ)
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