Congratulations to Matt Grubb for receiving a Research Grant from the International Foundation for Research in Paraplegia (IRP), with the aim of exploiting neuronal plasticity to promote functional recovery after nerve regeneration.
In order to treat paraplegia and other neurological disorders, we not only need to re-establish projections in the damaged nervous system, but also ensure that any restored projections can connect appropriately with, and are fully functionally integrated into, their target networks. A crucial player in these processes is neuronal plasticity – the ability of cells and networks to adapt to alterations in their inputs. It is known that neuronal circuits can undergo considerable plastic changes following injury, and that some of this plasticity can be leveraged by training programmes to improve functional recovery. However, what is not understood is the plasticity within neuronal networks that is required to maximise the functional impact of axonal regrowth. To tackle this crucial issue requires an opportunity to study this process as it occurs naturally. This would allow us to ask the following question: When axonal regrowth occurs naturally in the nervous system, how does plasticity in target networks enable its functional integration? Once we have detailed knowledge of this process, the hope is that we can then extend its mechanisms and general principles to optimise the functional impact of regenerating axons in paraplegia and other disorders.
"We will take this exact approach in our IRP-funded research, exploiting the astonishing natural regenerative capacity of the mammalian olfactory system.”
The olfactory nerve, which connects sensory neurons in the nose with the first centre for smell processing in the brain, is naturally capable of wholescale regrowth after injury, toxicity or infection. Importantly, this regenerated nerve re-wires anatomically and functionally to appropriate targets, and can produce full behavioural recovery. Such functional regeneration requires new axon terminals to connect appropriately with target circuitry, and these freshly re-connected networks to adapt to their regenerated sensory input. The olfactory nerve’s target structure, the olfactory bulb, is a particularly adaptable part of the brain, so plastic changes in its circuits could be a major contributor to functional recovery from olfactory nerve injury. However, surprisingly little is understood about olfactory bulb network function and plasticity following damage and regrowth of the olfactory nerve.
"Our IRP-funded project aims to address this important gap in our knowledge by describing the plastic alterations made by olfactory bulb circuits to optimise functional recovery during the natural regeneration of their inputs. In doing so, we aim to identify novel, plasticity-based therapeutic strategies for promoting successful re-wiring and integration of other connections in the nervous system, including spinal cord circuits in paraplegia."