Role of astrocytes in Ca2+- dependent microglia modulation of synaptic activity
Abstract
"The roles of intracellular microglia Ca2+ dynamics in CNS function remain unknown. In particular, it is unclear what factors drive Ca2+ transients in microglia processes and whether Ca2+ transients in microglia drive the process motility observed in vivo. It is also unknown if Ca2+ transients and process movements play a role in the release of soluble factors that potentially modulate neuronal excitability. To date, the study of these issues has been hampered due to an inability to monitor intracellular microglia Ca2+ transients in intact animals. To address this problem, our group has generated floxed mice expressing GCaMP5G, as well as the Ca2+ insensitive tdTomato marker, to study the role of intracellular Ca2+ dynamics in microglia process extension and retraction. Our preliminary data using GCaMP5G animals and 2-photon Ca2+ imaging indicates that in the acute brain slice preparation application of ATP leads to an immediate rise in intracellular Ca2+ closely associated with microglia process movement. Similarly, our in vivo experiments in anesthetize animals also indicate a close association of microglia intracellular Ca2+ transients and processes movement. Using these techniques in combination with pharmacology, 2-photon Ca2+ imaging of astrocytes and intracellular recordings of nearby neurons, we expect to establish a role for microglia Ca2+ activity in the CNS. Given our preliminary data, we hypothesize that spontaneous release of ATP by astrocytes mediates Ca2+-dependent extension and/or retraction of microglial processes. Through this mechanism, microglia processes can respond to sensory-evoked neural activity, come into physical contact with neurons, and release soluble factors that modulate synaptic transmission. The proposed studies have the" "to define new and various roles for microglia in neuromodulaton"
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jul 09, 2020
- Source ID
- W911NF2010189
Entities
People
- N. J. H. Smith
Organizations
- Army Contracting Command
- United States Army