Final Report Summary - HOMEOSTASIS_IN_VIVO (Mechanisms of homeostatic plasticity in the intact mouse visual cortex)
The brain has homeostatic mechanisms in place that prevent brain activity from becoming too high or too low. Because activity in our brains is often changing due to the ongoing changes in the inputs from the world around us, or because the brain is adapting in response to learning or creating memories, these homeostatic mechanisms are necessary to rebalance activity levels into the appropriate physiological range. In this grant, we have investigated the spatial scales in which these homeostatic mechanisms are implemented in the brain and how these different mechanisms help rebalance activity levels when they have deviated from typical. Because homeostatic plasticity is disrupted in many disease states – for example, Alzheimer’s disease, schizophrenia, forms of mental disability and epilepsy - understanding the spatial level that these homeostatic mechanisms are implemented is critical for developing targets for treatments when these mechanisms are disrupted in disease states. We found that homeostatic adjustments can happen at many different spatial levels - at the level of individual synapses, within a dendrite, cells or networks of cells. We found that these changes happen in different cell types as well, both those that lead to excitatory and inhibitory activity. These changes interact to influence the overall activity levels and allow the brain to rebalance activity after there has been a loss of input. Overall, our studies have implicated that networks of cells in the brain and the activity that is intrinsic to the brain is critical for the homeostatic rebalancing of activity. We developed a number of new experimental approaches, extending several state-of-the-art techniques in order to address these questions, including new analysis techniques and new approaches to identify cells in the brain that are changing their activity levels for brain plasticity. In future studies, we can use these approaches to further our understanding of different forms of plasticity in the brain.