miR-132 Enhances Dendritic Morphogenesis, Spine Density, Synaptic Integration, and Survival of Newborn Olfactory Bulb Neurons

TLDR

Early postnatal SVZ neurogenesis is regulated by many signals, but the molecular regulators of late-stage development remain poorly understood. The study examined how the activity‑dependent microRNA miR‑132 influences synaptic integration and survival of newborn olfactory bulb neurons derived from the neonatal SVZ. In vivo electroporation was used to overexpress or sponge miR‑132 in these newborn neurons. miR‑132 is expressed at the onset of synaptic integration, and its overexpression increases dendritic complexity, spine density, excitatory and inhibitory synaptic input, and neuronal survival, whereas sequestration has the opposite effect, indicating that miR‑132 drives structural plasticity in postnatal SVZ‑OB neurogenesis and may enhance transplant outcomes.

Abstract

An array of signals regulating the early stages of postnatal subventricular zone (SVZ) neurogenesis has been identified, but much less is known regarding the molecules controlling late stages. Here, we investigated the function of the activity-dependent and morphogenic microRNA miR-132 on the synaptic integration and survival of olfactory bulb (OB) neurons born in the neonatal SVZ. In situ hybridization revealed that miR-132 expression occurs at the onset of synaptic integration in the OB. Using in vivo electroporation we found that sequestration of miR-132 using a sponge-based strategy led to a reduced dendritic complexity and spine density while overexpression had the opposite effects. These effects were mirrored with respective changes in the frequency of GABAergic and glutamatergic synaptic inputs reflecting altered synaptic integration. In addition, timely directed overexpression of miR-132 at the onset of synaptic integration using an inducible approach led to a significant increase in the survival of newborn neurons. These data suggest that miR-132 forms the basis of a structural plasticity program seen in SVZ-OB postnatal neurogenesis. miR-132 overexpression in transplanted neurons may thus hold promise for enhancing neuronal survival and improving the outcome of transplant therapies.