Document - In vivo single branch axotomy induces GAP-43-dependent sprouting and synaptic remodeling in cerebellar cortex

2013

Journal article Open Access

In vivo single branch axotomy induces GAP-43-dependent sprouting and synaptic remodeling in cerebellar cortex

Mascaro Anna Letizia Allegra, Cesare Paolo, Sacconi Leonardo, Grasselli Giorgio, Mandolesi Georgia, Maco Bohumil, Knott Graham W., Huang Lieven, De Paola Vincenzo, Strata Piergiorgio, Pavone Francesco S.

Neural plasticity Neurological GAP-43 Protein Transgenic brain injury Axotomy RNA Interference laser nanosurgery Imaging Cerebellar Cortex Presynaptic Terminals Imaging, Three-Dimensional Two-photon imaging Multidisciplinary Biological Sciences neural plasticity Mice, Transgenic Nerve Regeneration Axons two-photon imaging Laser nanosurgery Animals Neuronal Plasticity Mice Models Models, Neurological Nerve Degeneration Nerve Fibers Three-Dimensional Brain injury

Plasticity in the central nervous system in response to injury is a complex process involving axonal remodeling regulated by specific molecular pathways. Here, we dissected the role of growth-associated protein 43 (GAP-43; also known as neuromodulin and B-50) in axonal structural plasticity by using, as a model, climbing fibers. Single axonal branches were dissected by laser axotomy, avoiding collateral damage to the adjacent dendrite and the formation of a persistent glial scar. Despite the very small denervated area, the injured axons consistently reshape the connectivity with surrounding neurons. At the same time, adult climbing fibers react by sprouting new branches through the intact surroundings. Newly formed branches presented varicosities, suggesting that new axons were more than just exploratory sprouts. Correlative light and electron microscopy reveals that the sprouted branch contains large numbers of vesicles, with varicosities in the close vicinity of Purkinje dendrites. By using an RNA interference approach, we found that downregulating GAP-43 causes a significant increase in the turnover of presynaptic boutons. In addition, silencing hampers the generation of reactive sprouts. Our findings show the requirement of GAP-43 in sustaining synaptic stability and promoting the initiation of axonal regrowth.

Source: Proceedings of the National Academy of Sciences of the United States of America 110 (2013): 10824–10829. doi:10.1073/pnas.1219256110

Publisher: The Academy,, Washington, D.C. , Stati Uniti d'America

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@article{oai:it.cnr:prodotti:294089,
	title = {In vivo single branch axotomy induces GAP-43-dependent sprouting and synaptic remodeling in cerebellar cortex},
	author = {Mascaro Anna Letizia Allegra and Cesare Paolo and Sacconi Leonardo and Grasselli Giorgio and Mandolesi Georgia and Maco Bohumil and Knott Graham W. and Huang Lieven and De Paola Vincenzo and Strata Piergiorgio and Pavone Francesco S.},
	publisher = {The Academy,, Washington, D.C. , Stati Uniti d'America},
	doi = {10.1073/pnas.1219256110},
	journal = {Proceedings of the National Academy of Sciences of the United States of America},
	volume = {110},
	pages = {10824–10829},
	year = {2013}
}