Principles of post-injury remodeling of excitatory and inhibitory locomotor circuits
Functional recovery after injuries to the central nervous system critically depends on the post-injury remodelling of axonal circuits. In the previous funding period we have identified important molecular cues that trigger the formation of contacts from the corticospinal tract onto target cells and have established that neuronal activity of the post-synaptic neuron shapes the formation of post-injury detour circuits. In this funding period we want to further unravel the common principles that regulate the remodeling of locomotor circuits. For this purpose we want to focus our investigations on the reticulospinal tract that plays an essential role in locomotion. Its dual structure containing both excitatory and inhibitory fibers provides a unique paradigm to compare the structural and functional adaptation of distinct transmitter system following injury. We will use circuit mapping including retrograde monosynaptic tracing, in combination with targeted genetic silencing and 3D imaging to identify, (i) additional molecular regulators of axonal remodelling (ii) how the excitatory and inhibitory axonal components of the reticulospinal tract remodel following spinal cord injury and the contribution of these axonal components to functional recovery and potential unwanted side effects and (iii) if and how these distinct tract components can be targeted by therapeutic intervention.