Grant: Operating Grant

Neural circuits have a remarkable challenge within the brain. They need to be stable in order to preserve important information while at the same time have enough flexibility to accommodate new information. An imbalance of these processes leads to inefficient brain function and likely plays a significant role in diseases such schizophrenia and depression. In recent years, much has been learned about mechanisms that contribute to brain plasticity, especially at the level of synapses, the specialized sites of connection between two neurons within a brain circuit. Changes in the ability of neurons to release or detect neurotransmitter are known to change the efficiency and strength of synaptic transmission. Homeostatic mechanisms are also enlisted to adjust the properties of synaptic connections to ensure that the activity of neurons remains within a useful working range (not too high or too low). Thus, an important balance of plasticity and homeostasis is needed to support proper brain activity. Despite our knowledge of these diverse plasticity mechanisms, the cellular and molecular events that underlie these processes are not fully understood and remain an important focus of neuroscience research. New discoveries have found that astrocytes, a type of glial cell in the brain, play an important role in synaptic transmission and plasticity. However, we are only beginning to understand how astrocytes regulate the function of neurons and neural circuits to modify and preserve brain function. In this grant renewal, we will combine in vivo and in vitro analysis using a range of genetic, molecular, biochemical, imaging, behavioral, electrophysiological and optogenetic approaches to uncover how neurons and astrocytes intercommunicate. This grant will provide fundamental information about how the brain encodes information and reveal important clues and potential therapeutic avenues for treating conditions where disregulation of neural circuits and brain function occurs.