Astrocytes represent about 40-60% of the cells in the brain and cover the entire nervous system, displaying bushy morphologies that comprise thousands of branches and branchlets. Neighboring astrocytes overlap minimally at their edges, but the tips of adjacent astrocytes meet and are coupled intracellularly via specialized regions called gap junctions. These intercellular conduits permit fast electrical coupling and the exchange of small solutes through a syncitium of astrocytes coupled over long distances. Spectacular advances have shown that astrocytes perform fundamental roles in the formation, removal, regulation and plasticity of synapses. However, the possibility that coupled astrocyte networks can contribute to the integrative properties of neuronal networks assembled into local microcircuits remains largely unexplored. Oscillations in the local field potential in the gamma-band (20-100 Hz, gamma oscillations) are a neuronal network phenomenon that occurs during cognitive processes. The CA3 region of the hippocampus is an established model microcircuit to experimentally explore the origins and regulation of gamma activity. Precisely timed and tightly correlated excitatory and inhibitory neuronal activity and neuronal gap junctions are critical for gamma oscillations, but little is known about how intermingled astrocytes regulate oscillations. Pioneering recent studies suggest that astrocytes affect gamma oscillations via release of the neurally active substances. These studies raise the possibility that gap junctions may represent a mechanism for regulating gamma oscillations in small microcircuits within the astrocyte syncytium. I will test the hypothesis that astrocyte coupling via gap junctions is permissive for hippocampal gamma oscillations and that disruption of gap junction coupling disrupts normal network activity in the hippocampus. This will be accomplished by rigorously testing a novel method for effectively reducing gap junction coupling in hippocampal astrocytes, and determining the effects of reduced coupling on gamma oscillations. Cognitive decline has been linked with disrupted gamma oscillations in several neurological and psychiatric disorders including schizophrenia, Alzheimer's disease, epilepsy, and attention-deficit hyperactivity disorder. Hence, understanding astrocyte gap junction function in the normal brain will provide unique opportunities to explore astrocyte roles not only in basic neural circuit properties, but also in the context of disease states.
Astrocytes, a type of brain cell that make up roughly half of the cells in brain, provide metabolic support to neurons and regulate neuronal activity. They also express proteins that allow them to transmit signals from cell-to-cell, forming a network that has been implicated in traumatic brain injury and epilepsy. Studying this network and how it regulates neuronal activity will provide insight into how astrocytes are involved in neurological diseases.
