Final Report Summary - RECORTHA (Rewiring cortical areas through thalamocortical inputs)
Research into neuroplasticity has expanded rapidly over the past ten years and it has revealed the remarkable capacity of environmental inputs to shape both the juvenile and adult brain. In particular, striking effects of sensory deprivation in one modality on the development of the remaining modalities have been documented in a wealth of studies. For instance, the loss of receptor arrays or sensory driven activity in the auditory or visual system, as occurs in congenitally deaf and blind individuals, produces tremendous alterations in cortical organization such that the deprived regions of the cortex are activated by different sensory stimuli. Furthermore, we know that this reorganized cortex appears to be functionally optimized in humans since the discriminatory and perceptual abilities of the spared sensory systems are enhanced. However, the challenge remains to recognize the mechanisms that control this rewiring, which will be essential to efficiently restore function to sensory deprived cortical areas. Interestingly, the appropriate delivery of electrical stimulation to intact visual structures can evoke patterned sensations of light in those who have been blind for many years.
The specialized functions of the different neocortical areas depend on the innervation pattern from the thalamus, as virtually all the information we receive from the outside world passes through the thalamus to the cerebral cortex, including visual, auditory and somatosensory stimuli. In this Project we are adopting a unique multidisciplinary approach (from gene to behaviour) to determine how thalamocortical wiring influences and maintains the functional architecture of the brain, and to what extent rewiring and plasticity can be triggered by activity dependent mechanisms in the thalamus. This novel frontier research will provide a detailed understanding of how thalamocortical neuronal activity influences cortical wiring, helping to predict the effects of sensory deprivation in the adult. It will also open up new horizons for the regeneration and repair of nervous tissue. Accordingly, we may be able to test whether the appropriate delivery of electrical stimulation to intact thalamic structures could evoke patterned sensations in sensory deprived areas, or whether specific manipulation of the thalamus within a specific time-window might increase the success of restoring sensory input with prosthetic devices.
During the consecution of this project we have found that spontaneous electrical activity and its associated calcium transients are crucial for the correct formation of the thalamocortical connectivity. As development proceeds, it appears necessary for axons approaching their targets to reduce their rate of extension in order to explore potential synaptic areas more thoroughly. We found that modifications to spontaneous calcium activity encode a switch in the axon outgrowth program that allows the establishment of specific neuronal connections. This activity dependent modulation of growth occurs by regulating the transcription two genes with antagonistic functions, a brake and an accelerator, for axonal growth. The present data have important implications for our understanding of how the brain is wired, as well as open novel perspectives that should be considered when contemplating axon regeneration and repair. Moreover, we have developed new tools to modify thalamic spontaneous activity and sensory systems development in vivo. By using these tools we will determine the role of thalamocortical input in cortical development and plasticity.
The specialized functions of the different neocortical areas depend on the innervation pattern from the thalamus, as virtually all the information we receive from the outside world passes through the thalamus to the cerebral cortex, including visual, auditory and somatosensory stimuli. In this Project we are adopting a unique multidisciplinary approach (from gene to behaviour) to determine how thalamocortical wiring influences and maintains the functional architecture of the brain, and to what extent rewiring and plasticity can be triggered by activity dependent mechanisms in the thalamus. This novel frontier research will provide a detailed understanding of how thalamocortical neuronal activity influences cortical wiring, helping to predict the effects of sensory deprivation in the adult. It will also open up new horizons for the regeneration and repair of nervous tissue. Accordingly, we may be able to test whether the appropriate delivery of electrical stimulation to intact thalamic structures could evoke patterned sensations in sensory deprived areas, or whether specific manipulation of the thalamus within a specific time-window might increase the success of restoring sensory input with prosthetic devices.
During the consecution of this project we have found that spontaneous electrical activity and its associated calcium transients are crucial for the correct formation of the thalamocortical connectivity. As development proceeds, it appears necessary for axons approaching their targets to reduce their rate of extension in order to explore potential synaptic areas more thoroughly. We found that modifications to spontaneous calcium activity encode a switch in the axon outgrowth program that allows the establishment of specific neuronal connections. This activity dependent modulation of growth occurs by regulating the transcription two genes with antagonistic functions, a brake and an accelerator, for axonal growth. The present data have important implications for our understanding of how the brain is wired, as well as open novel perspectives that should be considered when contemplating axon regeneration and repair. Moreover, we have developed new tools to modify thalamic spontaneous activity and sensory systems development in vivo. By using these tools we will determine the role of thalamocortical input in cortical development and plasticity.