Grant: Discovery Grants Program - Individual

Performing a bout of cardiorespiratory exercise has widespread effects on the central nervous system. For many years, researchers focused on studying how post-exercise changes in arousal could transiently increase mental task performance (e.g., attention, information processing). While involvement of multiple molecular signaling pathways in these effects were identified, a particularly important influence of catecholamines, such as dopamine, was established. More recently, there has been a shift towards consideration of whether acute exercise effects on the brain might also influence neuroplasticity to promote more lasting neural changes, such as those involved in learning and memory. Notably, dopamine is a modulator of neuroplasticity, with complex actions that can both facilitate or suppress neuroplasticity depending on neuronal activity and dopamine sub-receptor activation. However, the role of dopamine in contributing to exercise-induced changes in neuroplasticity is not yet well characterized. Here, I propose a research program that investigates how the physiological effects of cardiorespiratory exercise interact with neuroplasticity in humans. Short-term research objectives will focus on studying the potential role of the dopaminergic system in contributing to acute exercise effects on neuroplasticity through a series of five projects. In these projects, response to plasticity-inducing non-invasive brain stimulation protocols targeting the motor cortex will be used to index neuroplasticity immediately after cardiorespiratory exercise or control conditions. In the first project, a candidate gene analysis will examine how genetic variation impacting dopaminergic signaling relates to exercise-induced changes in neuroplasticity, determined by a technique termed excitatory paired associative stimulation. In the second and third projects, participants will perform varied intensities of cardiorespiratory exercise and receive varied doses of dopamine precursor drug (levo-dopa) prior to excitatory paired associative stimulation. This approach will allow direct investigation of interactions between exercise and dopaminergic effects on neuroplasticity. In the fourth and fifth projects, the acute effects of exercise on different forms of neuroplasticity known to be uniquely impacted by dopaminergic activity will be characterized. These projects will involve the use of paired associative stimulation and transcranial direct current stimulation techniques, which induce focal, associative, and non-focal, non-associative neuroplasticity, respectively. This work will provide key advances in mechanistic understanding of acute cardiorespiratory exercise effects on human neuroplasticity, setting the stage for a long-term research program considering interactions between different types of exercise, molecular signaling pathways, brain regions, and forms of neuroplasticity.