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Stereotactic Injection of MicroRNA-expressing Lentiviruses to the Mouse Hippocampus CA1 Region and Assessment of the Behavioral Outcome
Published on: June 10, 2013
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MicroRNA-138 controls hippocampal interneuron function and short-term memory in mice.
Reetu Daswani1, Carlotta Gilardi1, Michael Soutschek1
1Lab of Systems Neuroscience, Institute for Neuroscience, Department of Health Science and Technology, Swiss Federal Institute of Technology ETH, Zurich, Switzerland.
Elife
|March 15, 2022
Summary
MicroRNA-138-5p regulates short-term memory and inhibitory neuron function. Its inactivation in parvalbumin interneurons impairs memory and alters synaptic transmission, impacting brain development and schizophrenia risk.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Neuronal circuit function depends on balanced excitatory/inhibitory (E/I) transmission.
- Disrupted E/I balance is linked to neurodevelopmental disorders like schizophrenia.
- MicroRNA (miRNA) roles in pyramidal neurons are known, but their function in inhibitory interneurons is unclear.
Purpose of the Study:
- Investigate the role of miR138-5p in regulating inhibitory interneuron function.
- Determine the impact of miR138-5p on synaptic transmission and cognitive behavior.
- Identify miR138-5p target genes involved in neural circuit regulation.
Main Methods:
- Sponge-mediated inactivation of miR138-5p in mouse parvalbumin (PV)-expressing interneurons.
- Assessment of spatial recognition memory and GABAergic synaptic input.
- Validation of Erbb4 as a direct miR138-5p target gene.
Main Results:
- miR138-5p inactivation in PV interneurons impaired spatial recognition memory.
- Inactivation enhanced GABAergic synaptic input onto pyramidal neurons.
- Schizophrenia-associated Erbb4 was identified as a direct miR138-5p target and was upregulated upon inactivation.
Conclusions:
- miR138-5p is a critical regulator of PV interneuron function and cognitive processes in mice.
- Dysregulation of miR138-5p in interneurons has implications for schizophrenia.
- MicroRNAs fine-tune both excitatory and inhibitory synaptic transmission, orchestrating neural circuit development.

