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.

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.


All our experiments use high resolution patch-clamp electrophysiology in combination with distinct imaging techniques. The main imaging methods in the lab include: total internal reflection fluorescence (TIRF) microscopy, FRET microscopy, single molecule imaging, spectroscopy, 2-photon microscopy as well as standard confocal and epifluorescence microscopy. The lab also uses molecular biology methods to engineer receptors, channels and calcium sensors to refine or improve their performance. Mouse genetics is being used to express optical sensors in vivo in the brain.