miR-132 enhances dendritic morphogenesis, spine density, synaptic integration, and survival of newborn olfactory bulb neurons.
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.
Department of Neurosurgery, Yale University School of Medicine, New Haven, Connecticut, United States of America.
Manavendra
M
Pathania
Juan
J
Torres-Reveron
Lily
L
Yan
Tomoki
T
Kimura
Tiffany V
TV
Lin
Valerie
V
Gordon
Zhao-Qian
ZQ
Teng
Xinyu
X
Zhao
Tudor A
TA
Fulga
David
D
Van Vactor
Angélique
A
Bordey
D000818:Animals; D000831:Animals, Newborn; D002470:Cell Survival / Q000235:genetics; D002552:Cerebral Ventricles / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D049229:Dendritic Spines / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D055785:Gene Knockdown Techniques; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D055495:Neurogenesis / Q000235:genetics; D009473:Neuronal Plasticity / Q000235:genetics; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D009830:Olfactory Bulb / Q000166:cytology* / Q000254:growth & development; D013569:Synapses / Q000235:genetics / Q000378:metabolism*
D017362:Cyclic AMP Response Element-Binding Protein; C546976:MIRN132 microRNA, mouse; D035683:MicroRNAs