Biology subjects

Daswani, R.

Publications and source records attributed to Daswani, R..

2 recordsLinked to original sources

bioRxiv2024

microRNA-138-5p suppresses excitatory synaptic strength at the cerebellar input layer

MicroRNAs are small, highly conserved non-coding RNAs that negatively regulate mRNA translation and stability. In the brain, microRNAs contribute to neuronal development, synaptogenesis, and synaptic plasticity. The microRNA 138-5p (miR-138-5p) controls inhibitory synaptic transmission in the hippocampus and is highly expressed in cerebellar excitatory neurons. However, its role in cerebellar synaptic transmission remains unkwown. Here, we investigated excitatory transmission within the cerebellum in mice expressing a sponge construct that sequesters endogenous miR-138-5p. Mossy fiber stimulation-evoked excitatory postsynaptic currents (EPSCs) in granule cells were significantly larger compared with controls. Furthermore, we observed larger miniature EPSC amplitudes, suggesting increased postsynaptic AMPA receptor numbers. High-frequency train stimulations revealed enhanced short-term depression following miR-138-5p downregulation. Together with computational modelling, this suggests a negative regulation of presynaptic release probability. Overall, our results demonstrate that miR-138-5p suppresses synaptic strength through pre- and postsynaptic mechanisms, providing a powerful mechanism for tuning excitatory synaptic input into the cerebellum.

neuroscience↗

bioRxiv2021

microRNA-138 controls hippocampal interneuron function and short-term memory

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 miR-138-5p as a regulator of short-term memory and inhibitory synaptic transmission in the hippocampus. Sponge-mediated miR-138-5p inactivation specifically in parvalbumin (PV)-expressing interneurons impairs spatial recognition memory and enhances GABAergic synaptic input onto pyramidal neurons. Cellular and behavioural phenotypes associated with miR-138-5p inactivation are paralleled by an upregulation of the schizophrenia-associated Erbb4, which we validated as a direct miR-138-5p target gene. Our findings suggest that miR-138-5p is a critical regulator of PV interneuron function, 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.

neuroscience↗