Roles of astrocytes in the brain. Astrocytes are a type of brain glial cell. In 1899 Cajal showed the close
spatial relationships between astrocytes and neurons in the brain. Subsequent anatomical work a century later showed that a single hippocampal
astrocyte can form connections with ~100,000 synapses and that individual astrocytes are tiled in non-overlapping domains. Moreover, astrocytes
are known to release signaling molecules through a variety of mechanisms. These studies raise the possibility that astrocytes may regulate
neuronal function. A major project in the lab seeks to investigate this possibility in the context of neuronal networks in the healthy brain
as well as for models of Huntington's disease.
Neuromodulation by P2X receptors in the brain. In the past we devoted considerable effort to exploring structure-function
relationships in P2X receptors. One major new direction that we have decided to take is to explore the role of P2X receptors in neuronal
networks. By understanding how P2X receptors are trafficked, activated and regulated in hippocampal neurons and microglia we are exploring
how ATP shapes excitability and signaling. As part of this effort we are developing non-invasive in vivo FRET and single molecule imaging
approaches (with designer engineered receptors) to image receptor mobility, activation and trafficking in neurons and microglia over broad
spatial and temporal scales within intact neuronal networks.
Shigetomi, E. Tong, X. Kwan, K. Corey, D.P. & Khakh, B.S. (2011) TRPA1 mediated microdomains regulate astrocyte resting calcium levels and inhibitory synapse efficacy via GAT-3. Nature Neuroscience 15: 70-80.
Shigetomi, E. Kracun, S. Sofroniew, M. & Khakh, B.S. (2010) A genetically targeted optical sensor to monitor calcium signals in astrocyte processes. Nature Neuroscience 13: 759-766. PMCID PMC2920135
Richler, E. Chaumont, S. Shigetomi, E. Sagasti, A. & Khakh, B.S. (2008). Tracking transmitter-gated P2X cation channel activation in vitro and in vivo. Nature Methods 5: 87-93