Physiological role for amyloid precursor protein in adult experience-dependent plasticity.

Changes in neural circuits after experience-dependent plasticity are brought about by the formation of new circuits via axonal growth and pruning. Here, using a combination of electrophysiology, adeno-associated virus-delivered fluorescent proteins, analysis of mutant mice, and two-photon microscopy, we follow long-range horizontally projecting axons in primary somatosensory cortex before and after selective whisker plucking. Whisker plucking induces axonal growth and pruning of horizontal projecting axons from neurons located in the surrounding intact whisker representations. We report that amyloid precursor protein is crucial for axonal pruning and contributes in a cell autonomous way.

Large-scale axonal reorganization of inhibitory neurons following retinal lesions.

The functional properties of adult cortical neurons are subject to alterations in sensory experience. Retinal lesions lead to remapping of cortical topography in the region of primary visual cortex representing the lesioned part of the retina, the lesion projection zone (LPZ), with receptive fields shifting to the intact parts of the retina. Neurons within the LPZ receive strengthened input from the surrounding region by growth of the plexus of excitatory long-range horizontal connections. Here, by combining cell type-specific labeling with a genetically engineered recombinant adeno-associated virus and in vivo two-photon microscopy in adult macaques, we showed that the remapping was also associated with alterations in the axonal arbors of inhibitory neurons, which underwent a parallel process of pruning and growth. The axons of inhibitory neurons located within the LPZ extended across the LPZ border, suggesting a mechanism by which new excitatory input arising from the peri-LPZ is balanced by reciprocal inhibition arising from the LPZ.

Death receptor 6 regulates adult experience-dependent cortical plasticity.

Sensory experience alters cortical circuitry by parallel processes of axon outgrowth and pruning, but the mechanisms that control these rearrangements are poorly understood. Using in vivo 2-photon longitudinal imaging, we found a marked reduction in axonal pruning in somatosensory cortex of mice with a knock-out of the DR6 gene, which codes for Death Receptor 6. This effect was seen for both long-range horizontal excitatory connections and for the axons of inhibitory neurons. These results identify a new pathway governing axonal plasticity associated with experience-dependent changes in cortical maps.

Axonal dynamics of excitatory and inhibitory neurons in somatosensory cortex.

Cortical topography can be remapped as a consequence of sensory deprivation, suggesting that cortical circuits are continually modified by experience. To see the effect of altered sensory experience on specific components of cortical circuits, we imaged neurons, labeled with a genetically modified adeno-associated virus, in the intact mouse somatosensory cortex before and after whisker plucking. Following whisker plucking we observed massive and rapid reorganization of the axons of both excitatory and inhibitory neurons, accompanied by a transient increase in bouton density. For horizontally projecting axons of excitatory neurons there was a net increase in axonal projections from the non-deprived whisker barrel columns into the deprived barrel columns. The axon collaterals of inhibitory neurons located in the deprived whisker barrel columns retracted in the vicinity of their somata and sprouted long-range projections beyond their normal reach towards the non-deprived whisker barrel columns. These results suggest that alterations in the balance of excitation and inhibition in deprived and non-deprived barrel columns underlie the topographic remapping associated with sensory deprivation.