The regulation of synaptic transmission. In particular we are interested in the reciprocal signaling between synapses and astrocytes that is mediated by the release of chemical transmitters and how astrocytes regulate synapses development and function.
Fluorescence microscopy, confocal microscopy, near-field microscopy, electrophysiology, patch clamp recording, calcium imaging, photolytic uncaging, cell and tissue culture, cell and molecular biology.
My research laboratory is interested in understanding the dynamic regulation of synaptic transmission and in elucidating the roles of glial cells in controlling the synapse. In many regions of the central nervous system it is apparent that synapses are tripartite structures in which in addition to the pre and postsynaptic terminal, the astrocyte (a sub-type of glial cell) acts as a third element that wraps around the synaptic structure. Recent studies are changing the view of the role of astrocytes in synaptic transmission. It is now clear that synaptic activity regulates calcium levels in astrocytes, and as a consequence of elevated calcium, we have demonstrated that astrocytes release the chemical transmitter glutamate onto the synapse to modulate synaptic transmission.
In order to understand the role of the astrocyte in the control of the synapse we are using photolysis to manipulate calcium levels within astrocytes while monitoring synaptic transmission. As another approach to study this complex system, we have developed selective inhibitors of the astrocytic glutamate release pathway and are using viral vectors to manipulate the release of this transmitter to determine the role of these glial cells in information processing. Using the hippocampal slice preparation (see figure) and optical approaches, we have recently demonstrated that transmitter-evoked calcium elevations in an astrocyte propagating to neighboring astrocytes as a calcium wave. This raises the possibility that a synapse could signal to neighbors by way of calcium signal that spreads through an astrocytic intermediate.
In addition to multi-cellular studies of the synapse, we also investigate the functional sub-structure of synapses using scanning probe microscopy. We have previously studied channel organization using atomic force microscopy and are currently using biological near-field microscopy, with optical resolution of 50 nm, to probe the workings of the synapse. Using this high-resolution system we are studying the local microdomains of calcium accumulation beneath activated calcium channels with the long-term objective of visualizing individual molecules within functional synapses to unravel the mysterious workings of this essential structure of the nervous system.
Haydon, P.G. (2001). Glia: Listening and Talking to the Synapse. Nature Reviews Neuroscience. 2: 185-193.
Araque, A., Carmignoto, G., and Haydon, P.G (2001). Dynamic Signaling Between Astrocytes and Neurons. Annual Reviews of Physiology. 63: 795-813.
Doyle, R.T., Szulzcewski, M.J., and Haydon, P.G. (2001) Extraction of near-field fluorescence from composite signals to provide high resolution images of glial cells. Biophys.J. 80: 2477-82.
Parpura, V., and Haydon, P.G.(2000) Physiological astrocytic calcium levels stimulate glutamate release to modulate adjacent neurons. Proc. Natl. Acad. Sci. USA 97: 8629-8634.
Araque, A., Li, N., Doyle, R.T. and Haydon, P.G. (2000) SNARE protein-dependent glutamate release from astrocytes. Journal of Neuroscience 20: 666-673.
Araque, A., Parpura, V., Sanzgiri, R. P., and Haydon, P.G. (1999) Tripartite Synapses: Glia, the unacknowledged partner. Trends in Neurosciences. 22: 208-215.
Araque, A., Sanzgiri, R.P., Parpura, V., and Haydon, P.G. (1998) Calcium elevation in astrocytes causes an NMDA receptor-dependent increase in the frequency of miniature synaptic currents in cultured hippocampal neurons. J. Neuroscience 18: 6822-6829.
Parpura, V., Basarsky, T.B., Liu, F., Jeftinija, S., Jeftinjia, S., and Haydon, P.G. (1994) Glutamate-mediated astrocyte-neuron signaling. Nature 369: 744-747.
Parpura, V., Basarsky, T.B., Liu, F., Jeftinija, S., Jeftinjia, S., and Haydon, P.G. (1994) Glutamate-mediated astrocyte-neuron signaling. Nature 369: 744-747.
Araque, A., Sanzgiri, R.P., Parpura, V., and Haydon, P.G. (1998) Calcium elevation in astrocytes causes an NMDA receptor-dependent increase in the frequency of miniature synaptic currents in cultured hippocampal neurons. J. Neuroscience 18: 6822-6829.
Araque, A., Parpura, V., Sanzgiri, R. P., and Haydon, P.G. (1999) Tripartite Synapses: Glia, the unacknowledged partner. Trends in Neurosciences. 22: 208-215.
Araque, A., Li, N., Doyle, R.T. and Haydon, P.G. (2000) SNARE protein-dependent glutamate release from astrocytes. Journal of Neuroscience 20: 666-673.
Parpura, V., and Haydon, P.G.(2000) Physiological astrocytic calcium levels stimulate glutamate release to modulate adjacent neurons. Proc. Natl. Acad. Sci. USA 97: 8629-8634.
Doyle, R.T., Szulzcewski, M.J., and Haydon, P.G. (2001) Extraction of near-field fluorescence from composite signals to provide high resolution images of glial cells. Biophys.J. 80: 2477-82.
Araque, A., Carmignoto, G., and Haydon, P.G (2001). Dynamic Signaling Between Astrocytes and Neurons. Annual Reviews of Physiology. 63: 795-813.
Haydon, P.G. (2001). Glial: Listening and Talking to the Synapse. Nature Reviews Neuroscience. 2: 185-193.
Haydon, P.G. Biological Near-Field Microscopy. (2003) Methods in Enzymology. Volume 360, Biophotonics, Part A. eds. Marriott, G. and Parker, I. Academic Press. 501-508.
Li, N., Sul, J.-Y. and Haydon, P.G. (2003) A Calcium-Induced Calcium Influx Factor, Nitric Oxide, Modulates the Refilling of Calcium Stores in Astrocytes. The Journal of Neuroscience 23(32): 10302-10.
Pascual O., Haydon P.G. (2003) Synaptic inhibition mediated by glia. Neuron 40(5): 873-5.
Sul, J.-Y., Orosz, G., Givens, R.S. and Haydon, P.G. (2004) Astrocytic Connectivity in the Hippocampus. Neuron Glia Biology 1, 3-11.
Zhang Q, Pangršic T, Kreft M, Kržan M, Li N, Sul JY, Halassa M, Van Bockstaele E, Zorec R, Haydon PG. (2004) Fusion-related release of glutamate from astrocytes. J. Biol. Chem.
Zhang, Q., and Haydon P.G (2004) Roles for gliotransmission in the nervous system. J. Neural Transmission. In Press.
Fedoryak, O., Sul, J-Y., Haydon, P.G. and Ellis-Davies, G.C.R. Synthesis of a caged glutamate for efficient one and two-photon photorelease on living cells. Chemical Communications. In Press.
Evanko, D. and Haydon, P.G. Environmental sensitivity of a cameleon FRET-based calcium sensor corrected with Venus SEYFP. Cell Calcium In Press.
Kreft, M., Stenovec, M., Rupnik, M., Grilc, S., Kržan, M., Potokar, M., Pangršic, T., Haydon, P.G. and Zorec, R. Properties of Ca2+-Dependent Exocytosis in Cultured Astrocytes. Glia (2004) May;46(4):437-45. Source .
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Philip G. Haydon 