Grant: Project Grant

A common feature in nearly all brain disorders and diseases is a breakdown in brain homeostasis. Key to brain homeostasis are highly specialized cells called astrocytes. Astrocytes play fundamental roles in brain function including controlling extracellular ion and neurotransmitter levels, brain energetics, and cerebrovasculature. Astrocytes perform diverse functions through their complex molecular, functional, structural properties. However, the mechanisms that create and sustain differences among astrocytes that allow them to fulfill unique physiological roles in the brain remain poorly understood. We discovered a completely new mechanism involving neurons for making different types of astrocytes in the brain. Communication between neurons and astrocytes enables astrocytes to produce key molecules including neurotransmitter transporters and receptors, adhesion molecules, potassium channels, and water channels. Thus, neurons in the mature brain control astrocytes to ensure that astrocytes acquire and maintain specialized properties that are precisely tuned to associated brain circuits. In this grant, we will determine how different astrocytes are created and maintained in the brain to support neuronal health and circuit function and identify how the properties of astrocytes can be harnessed to mitigate brain disorders and diseases.