New paper shows evidence for GAP-43-dependent regulation of presynaptic stability


We have a new collaborative paper with the Biophysics and Biophotonics groups at LENS in PNAS on GAP-43-depedent regulation of presynpatic sprouting.

In vivo single branch axotomy induces GAP-43-dependent sprouting and synaptic remodeling in cerebellar cortex.
Allegra-Mascaro, A. L., Cesare, P., Sacconi, L., Grasselli, G., Mandolesi, G., Maco, B., Knott, G., Huang, L, De Paola, V., Strata, P., Pavone, F. S.
Proceedings of the National Academy of Sciences of the United States of America 110, 10824-10829 (2013).

Plasticity in the central nervous system in response to injury is a complex process involving axonal remodeling regulated by specific molecular pathways.  In a this collaborative study with the Biphysics and Biophotonics groups at the European Laboratory for Non-Linear Spectroscopy (LENS) in Firenze, Italy, 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 (in which single axonal branches were dissected by laser axotomy, avoiding collateral damage to the adjacent dendrite and the formation of a persistent glial scar), and found that:

  • Adult climbing fibers reacted by sprouting new branches through the intact surroundings.
  • Newly formed branches presented varicosities, suggesting that new axons were more than just exploratory sprouts.
  • Downregulating GAP-43 caused a significant increase in the turnover of presynaptic boutons.

This study shows a requirement for GAP43 in regulating synaptic stability.

Figure 1 – In vivo imaging of climbing fibres (CFs). (A) Two Left panels show the two-photon fluorescence (TPF) transversal (maximum intensity z-projection of 60 images acquired from 0 to 120 μm deep below the pial surface) and sagittal view (digital rotation of the stack) of a single CF labeled by green fluorescent protein (GFP) expression in the cerebellar molecular layer. Right panel shows a confocal image of a single CF in a sagittal slice obtained from fixed cerebellum for comparison. CFs were labeled by GFP expression (green); Purkinje cells were labeled through immunofluorescent staining for Calbindin (in blue); CF varicosities in the molecular layer (together with some mossy fiber terminals in the granular layer) were labeled through immunofluorescent staining for VGlut2 (in red). C, caudal; D, dorsal; R, rostral; V, ventral. (B) Time-lapse images (TPF transversal view: maximum intensity z-projections) over a 12-d monitoring period showing the stability of CFs ascending branches. (Scale bar, 10 μm.)

PNAS-2013-110-10824-10829-figure-1-1000x1022

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