Impact of myelin dynamics on functional network stability and memory persistence

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A healthy brain will allow important memories to last for a long time and most everyday experiences to be forgotten. The establishment of brain-wide networks of coordinated nerve cell activation accompanies learning, and these networks are stabilized to support persistent memory and destabilized to cause forgetting. Plasticity the brain's ability to change is essential for network formation, stabilization and destabilization. The focus of most research has been on plasticity at the level of the connection points between nerve cells, where existing connections can be strengthened or weakened, as well as added or eliminated to form new networks or remodel existing ones. Axons are the long thin projections of nerve cells that conduct electrical impulses and allow for the integration of information between brain regions within networks. Precise timing of this information is crucial for network stability. Myelin, a component of support cells in the brain, insulates axons, thus the degree of myelination will affect the timing of electrical impulses. Myelination begins in the womb and progresses through childhood and adolescence and recent research has demonstrated that myelin keeps changing in adulthood. This brings to light another element of enduring plasticity changes in myelin whose influence on network stability and memory persistence is not known. The proposed research will focus on the influence of changes in myelin myelination during development and remodeling of myelin in adulthood on memory persistence and the stability of fear memory networks with the following short-term objectives: 1. To characterize the role of brain-wide myelin changes in fear memory persistence. 2. To model the effect of brain-wide myelin changes on fear memory network stability in a computer simulation. If the short-term objectives described here provide support for a specific role for myelin plasticity in memory persistence via network stability, many of the approaches can be translated to studies in humans in our lab. This is consistent with the long-term objective of our research program, which is to support translational studies about the relationships between brain structure and function across species. A better understanding of the mechanisms that underlie memory persistence and forgetting can lead to greater insight into how the brain optimizes memory function. This research program will provide the opportunity for trainees at all levels to acquire a broad range of research knowledge and technical skills. By uniting brain-wide network modelling, assessment of behaviour, genetic models that allow for manipulation of myelin, and MRI, this program will facilitate the acquisition of inter-disciplinary expertise that will prepare trainees for careers in neuroscience or biomedical research both within and outside of academia.