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MicroRNA-138 controls hippocampal interneuron function and short-term memory in mice
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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.
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“Erbb4 is a direct miR‐138‐5p target (Daswani et al., 2022) that has been implicated in pre‐ and postsynaptic function.”
From MicroRNA‐138‐5p suppresses excitatory synaptic strength at the cerebellar input layer (2025) · cites this paper as Daswani et al., 2022
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“On a behavioural level, loss of miR‐138‐5p impairs short‐term memory in mice, which is most probably the result of an increase in inhibitory transmission in area CA1 of the hippocampus (Daswani et al., 2022).”
From MicroRNA‐138‐5p suppresses excitatory synaptic strength at the cerebellar input layer (2025) · cites this paper as Daswani et al., 2022
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“Erbb4 has a prominent role in inhibitory hippocampal interneurons, where miR‐138 sponge expression caused an increase in inhibitory miniature event frequency (Daswani et al., 2022).”
From MicroRNA‐138‐5p suppresses excitatory synaptic strength at the cerebellar input layer (2025) · cites this paper as Daswani et al., 2022
In the citing paper
“On a behavioural level, loss of miR‐138‐5p impairs short‐term memory in mice, which is most probably the result of an increase in inhibitory transmission in area CA1 of the hippocampus (Daswani et al., 2022).”
From MicroRNA‐138‐5p suppresses excitatory synaptic strength at the cerebellar input layer (2025) · cites this paper as Daswani et al., 2022
In the citing paper
“MicroRNA 138‐5p (miR‐138‐5p) controls inhibitory synaptic transmission in the hippocampus and is highly expressed in cerebellar excitatory neurons.”
From MicroRNA‐138‐5p suppresses excitatory synaptic strength at the cerebellar input layer (2025) · cites this paper as Daswani et al., 2022
In the citing paper
“In inhibitory hippocampal interneurons, miR‐138‐5p may modulate synaptic transmission by inhibiting expression of the schizophrenia susceptibility gene Erbb4 (Erb‐B2 receptor tyrosine kinase 4) (Daswani et al., 2022).”
From MicroRNA‐138‐5p suppresses excitatory synaptic strength at the cerebellar input layer (2025) · cites this paper as Daswani et al., 2022
In the citing paper
“The direct miR‐138‐5p target Erbb4 (Daswani et al., 2022) is linked to both presynaptic and postsynaptic compartments (Koopmans et al., 2019) and is expressed in precerebellar nuclei from where mossy fibres originate.”
From MicroRNA‐138‐5p suppresses excitatory synaptic strength at the cerebellar input layer (2025) · cites this paper as Daswani et al., 2022
In the citing paper
“In the present study, inactivation of miR‐138‐5p increased mEPSC amplitudes in cerebellar GCs. This increase is probably mediated by increasing synaptic AMPAR numbers, which would be consistent with miR‐138‐5p targeting (and thus repressing) Erbb4, which in turn promotes GluA4 translation.”
From MicroRNA‐138‐5p suppresses excitatory synaptic strength at the cerebellar input layer (2025) · cites this paper as Daswani et al., 2022
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Citations
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Sorted by citations
Maza, R. M., Barreda-Manso, M. A., Reigada, D., Silván, Á., Muñoz-Galdeano, T., Soto, A., del Águila, Á., & Nieto-Díaz, M. (2022) · Biomedicines · doi:10.3390/biomedicines10071559 · Cited by 12
MicroRNA‐138‐5p suppresses excitatory synaptic strength at the cerebellar input layer
Delvendahl, I., Daswani, R., Winterer, J., Germain, P., Uhr, N. M., Schratt, G., & Müller, M. (2025) · The Journal of Physiology · doi:10.1113/jp288019 · Cited by 3
Self-citation
Metadata
- Authors
- Daswani, R., Gilardi, C., Soutschek, M., Nanda, P., Weiss, K., Bicker, S., Fiore, R., Dieterich, C., Germain, P.-L., Winterer, J., & Schratt, G.
- Affiliations
- Lab of Systems Neuroscience, Institute for Neuroscience, Department of Health Science and Technology, Swiss Federal Institute of Technology ETH
- Institute for Physiological Chemistry, Biochemical-Pharmacological Center Marburg, Philipps-University of Marburg
- Section of Bioinformatics and Systems Cardiology, Department of Internal Medicine III and Klaus Tschira Institute for Integrative Computational Cardiology, University of Heidelberg
- ORCID
- Venue
- eLife
- Publisher
- eLife Sciences Publications, Ltd
- Published
- 2022-03-15
- Volume
- 11
- ISSN
- 2050-084X
- PMC
- PMC8963876
- Cited by
- 38
- References
- 9
- Language
- en
- Licence
- Funders
- Deutsche Forschungsgemeinschaft (SCHR 1136/4-2)
- Eidgenössische Technische Hochschule Zürich (24 18-2 (NeuroSno))
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