The Role of Neural Activity in Enhancing Axon and Presynaptic Regeneration in the Adult Injured Neocortex In Vivo

点击翻译按钮获取中文摘要

The human brain is a highly complex system comprised of billions of neurons interconnected to each other to form functional neural circuits. Normal brain function is dependent on effective communication between neurons, a process that requires the establishment of synapses within the circuit. Several diseases that affect the brain result from impairments in the communication between neurons, which is why it is essential to understand how neural circuits are established and the mechanisms underlying circuit plasticity. We are particularly interested in understanding how the regeneration of neural circuits can be enhanced to restore connectivity and function after a brain lesion. Specifically, we aim to test the hypothesis that the activity of surviving neurons can elicit the regeneration of axons and synapses within the circuits, in order to overcome the functional deficits that result from an injury. We have previously demonstrated that certain populations of cortical neurons exhibit enhanced spontaneous regenerative capacity in comparison to others, and we are now interested in understanding the cellular and molecular mechanisms responsible for this differential response to injury between diverse neuronal populations. This knowledge will help us identify targets for future therapeutic interventions. With the prospect of developing strategies to enhance functional regeneration after injury, we will also manipulate neural activity by directly stimulating neurons within a circuit. Different stimulation protocols will be employed, in order to identify the parameters that are most effective in restoring structural and functional recovery. We will take advantage of powerful genetic, imaging and stimulation tools that allow manipulating neural activity and visualizing neurons in the living brain of laboratory animals. The ultimate aim of this research proposal is therefore to gain new and fundamental insights into the cellular and molecular mechanisms that regulate the regeneration of cortical neural circuits, in the hope that this knowledge will, in the future, translate into new ways to promote neural plasticity and functional recovery after brain injury.