Large-Scale Axonal Reorganization of Inhibitory Neurons following Retinal Lesions

Abstract

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.

Homeostatic Plasticity of Subcellular Neuronal Structures: From Inputs to Outputs

“…This was accompanied by an increase in excitatory bouton density, which contrasted with the decrease observed in interneurons. A similar pattern of axon growth was also found in the monkey primary visual cortex after focal binocular retinal lesions, where axons of pyramidal cells extended into the LPZ [44] and inhibitory neurons located inside the LPZ elongated their axons to project to the peri-LPZ [48]. It remains to be shown whether the interneurons projecting out of the LPZ form synaptic connections with those pyramidal cells that now project into the LPZ.…”

“…However, several elegant in vivo experiments have shown that axons and presynaptic boutons also have the capacity for change 30, 42, 43, 44, 45, 46, 47, 48 and often go hand in hand with postsynaptic plasticity.…”

Primary visual cortical remapping in patients with inherited peripheral retinal degeneration

“…The axonal sprouting and strengthening of long-range horizontal connections within V1 may lead to expansion and/or shifting of neuronal receptive fields into the cortical regions with altered retinal input. The inhibitory neuronal inputs inside the deprived visual cortex may be weakened, leading to an increase of excitatory horizontal connections with neurons in regions adjacent to the deprived region (Botelho et al, 2014, Butz and van Ooyen, 2013, Darian-Smith and Gilbert, 1995, Engel et al, 2015, Giannikopoulos and Eysel, 2006, Gilbert and Li, 2012, Marik et al, 2014, Pascual-Leone et al, 2005, Sammons and Keck, 2015, Shao et al, 2013, Wandell and Smirnakis, 2009, Yamahachi et al, 2009). Some authors have suggested the use of an artificial scotoma to mimic the patients' visual field extent, to help elucidate the origin of remapping (Goesaert et al, 2014, Masuda et al, 2010).…”

The connectomics of brain disorders

“…Animal models 94 and human studies 95 have shown that focal ischaemic damage can cause widespread depolarization of connected regions -particularly homotopic contralateral areas -resulting in persistent hyperexcitability or disinhibition of functionally related, but spatially distributed, networks 94,96 . Hyper excitability in these connected areas can be accompanied by increased synaptogenesis, and axonal and dendritic sprouting of undamaged axons [97][98][99][100] . This remodelling can take place over long distances, is activity-dependent 99,100 and can cause volumetric changes detectable with MRI 101 .…”