University of Tasmania, Australia

It is now recognised that the brain, rather than being static after childhood, is constantly adapting itself to changing conditions throughout adulthood and during physiological ageing. This neuroplasticity is believed to derive mainly from changes in synaptic transmission between neurons. There has been much recent interest in whether specific cognitive and motor skill training programs can promote neuroplasticity to slow, or even reverse, functional decline associated with ageing and promote recovery of function following brain damage. rTMS is a non-invasive method of modulating brain function, and involves applying complex pulse trains of magnetic fields through the skull. The rationale behind this project is that in vivo mouse experiments (to directly image changes in synaptic plasticity) in conjunction with tightly controlled human studies (testing effects of rTMS on motor learning tasks) will provide valuable new information that will inform clinical practice. A systematic program of translational research combining, for the first time in this field, psychologists and neuroscientists, will investigate the neurophysiological and neurobiological basis of an intervention that is being increasingly used to improve motor function in both healthy and compromised (e.g. disease/stroke) populations.

It has recently been established that motor learning in mice (as they master a new task) changes synaptic density in the primary motor cortex. While it is not possible to directly image synaptic plasticity in humans, we can implant glass windows in the cranium of transgenic mice expressing fluorescent reporter genes in neurons. We can then use two-photon laser scanning microscopy to repeatedly image the neuroplastic changes in the synapses of live mice. We train the mice in a variety of motor learning tasks, and apply rTMS to test whether this modulates task performance. Parallel studies with our colleagues in the School of Psychology at UTAS are testing rTMS protocols on equivalent motor learning tasks in human volunteers, and these two experimental streams inform each other bi-directionally. Additionally, once we have gathered data from these experiments, we will move on to test what differences exist in neuroplasticity in the motor cortex of aged mice. This will give crucial insight into the known loss of neuroplasticity which occurs during the normal ageing process, as well as in dementia.