MIR-138 CONTROLS HIPPOCAMPAL INTERNEURON FUNCTION AND SHORT-TERM MEMORY

The regulation of the balance between excitatory and inhibitory (E/I) neuronal synaptic transmission is essential for physiological circuit formation and function. MicroRNAs are a large family of post-transcriptional regulators and have been demonstrated to be pivotal in synapse development and plasticity. Their involvement in inhibitory interneuron function however is largely unknown. In this project, I found that the function of brain-enriched miR-138-5p in parvalbumin-expressing interneuron is required for short-term memory by using a cell-type specific miR-138-5p loss-of-function (“sponge”) model in mice. Cognitive deficits in miR-138-5p sponge mice are accompanied by increased inhibitory synaptic drive onto hippocampal CA1 pyramidal neurons and deregulated expression of mRNAs encoding for synaptic regulatory proteins. Our results expand the scope of microRNA function to the maintenance of proper E/I balance and suggest that these molecules could in the future be therapeutic targets in disorders where E/I balance is disrupted, such as autism and schizophrenia