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The neurotrophic factors of the nerve growth factor family (neurotrophins) have been shown to promote neuronal survival after brain injury and in various models of neurodegenerative conditions. However, it has not been determined whether neurotrophin treatment results in the maintenance of function of the rescued cells. Here we have used the retrograde degeneration of geniculate neurons as a model system to evaluate neuronal rescue and sparing of function after administration of brain-derived neurotrophic factor (BDNF). Death of geniculate neurons was induced by a visual cortex lesion in adult rats, and exogenous BDNF was delivered to the axotomized geniculate cells via anterograde transport after injection into the eye. By microelectrode recordings from the geniculate in vivo we have measured several physiological parameters such as contrast threshold, spatial resolution (visual acuity), signal-to-noise ratio, temporal resolution, and response latency. In control lesioned animals we found that geniculate cell dysfunction precedes the onset of neuronal death, indicating that an assessment of neuronal number per se is not predictive of functional performance. The administration of BDNF resulted in a highly significant cell-saving effect up to 2 weeks after the cortical damage and maintained nearly normal physiological responses in the geniculate. This preservation of function in adult axotomized neurons suggests possible therapeutic applications of BDNF.

Damage to the adult CNS often causes devastating and permanent deficits because of the limited capacity of the brain for anatomical reorganization. The finding that collateral sprouting of uninjured fiber tracts mediates recovery of function prompts the search for experimental strategies that stimulate axonal plasticity after CNS trauma. Here we characterize treatments that promote the sprouting of undamaged retinal afferents into the denervated superior colliculus (SC) after a partial retinal lesion in the adult rat. Delivery of brain-derived neurotrophic factor (BDNF) was performed to enhance the intrinsic potential of retinal ganglion cells to reelongate their axons. Reduction of the neurite growth-inhibitory properties of the adult SC was accomplished via treatment with chondroitinase ABC (C-ABC), which degrades chondroitin sulfate proteoglycans. Retinal axons were labeled via intraocular injections of fluorescently tagged cholera toxin B subunit, and fiber sprouting within the denervated SC was measured by quantitative laser-scanning confocal microscopy 1 week after the retinal lesion. We found that both the administration of BDNF and the injection of C-ABC induce significant sprouting of retinal afferents into the collicular scotoma. Remarkably, the combined treatment with BDNF and C-ABC showed synergistic effects on axon growth. Colocalization analysis with anti-synapsin antibodies demonstrated synapse formation by the sprouting axons. These results suggest that the combined treatment with BDNF and C-ABC can be relevant in therapies for the repair of the damaged adult CNS.

Vision is a very important sensory modality in humans. Visual disorders are numerous and arising from diverse and complex causes. Deficits in visual function are highly disabling from a social point of view and in addition cause a considerable economic burden. For all these reasons there is an intense effort by the scientific community to gather knowledge on visual deficit mechanisms and to find possible new strategies for recovery and treatment. In this review, we focus on an important and sometimes neglected player of the visual function, the corpus callosum (CC). The CC is the major white matter structure in the brain and is involved in information processing between the two hemispheres. In particular, visual callosal connections interconnect homologous areas of visual cortices, binding together the two halves of the visual field. This interhemispheric communication plays a significant role in visual cortical output. Here, we will first review the essential literature on the physiology of the callosal connections in normal vision. The available data support the view that the callosum contributes to both excitation and inhibition to the target hemisphere, with a dynamic adaptation to the strength of the incoming visual input. Next, we will focus on data showing how callosal connections may sense visual alterations and respond to the classical paradigm for the study of visual plasticity, i.e., monocular deprivation (MD). This is a prototypical example of a model for the study of callosal plasticity in pathological conditions (e.g., strabismus and amblyopia) characterized by unbalanced input from the two eyes. We will also discuss the findings of callosal alterations in blind subjects. Noteworthy, we will discuss data showing that inter-hemispheric transfer mediates recovery of visual responsiveness following cortical damage. Finally, we will provide an overview of how callosal projections dysfunction could contribute to pathologies such as neglect and occipital epilepsy. A particular focus will be on reviewing noninvasive brain stimulation techniques and optogenetic approaches that allow to selectively manipulate callosal function and to probe its involvement in cortical processing and plasticity. Overall, the data indicate that experience can potently impact on transcallosal connectivity, and that the callosum itself is crucial for plasticity and recovery in various disorders of the visual pathway.