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People / Haydon Laboratory![]() ContactPhilip Haydon, Ph.D.
Research InterestsIt is increasingly apparent that synapses are tripartite structures: 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 to control synapse formation and function. Goals of the laboratory are to identify the mechanisms by which astrocytes regulate synaptic transmission, neuronal circuits and their critical role in controlling behavior. Our recent studies also focus on the roles of these glial cells in disorders of the nervous system including epilepsy. Our interest in reciprocal signaling between astrocytes and neurons arose from the observation that Ca2+ oscillations in astrocytes lead to the release of chemical transmitters. Initially, we demonstrated that astrocytes can release the excitatory transmitter glutamate, and subsequent studies have shown that ATP and D-serine are also released from these synaptically associated glia. As a consequence, this process of gliotransmission modulates synaptic transmission. We use a variety of experimental strategies to study astrocyte-synapse interactions including molecular genetic manipulations of the astrocyte, in vivo and slice electrophysiology, two photon microscopy, and behavioral studies. In addition to studying synaptic transmission, we are now applying two photon microscopy to the study of the development of amyloid plaques in mouse models of Alzheimer’s disease. Using this technology we are able to repeatedly image the development of individual identified plaques and, using adeno-associated virus to selectively transduce neurons and or astrocytes, we observe and manipulate cellular signaling within neurons and glia to identify the roles of different cell types in the development of the disorder. Lab Members
Selected PublicationsDing S, Fellin T, Zhu Y, Lee SY, Auberson YP, Meaney DF, Coulter DA, Carmignoto G, Haydon PG. Enhanced astrocytic Ca2+ signals contribute to neuronal excitotoxicity after status epilepticus. J Neurosci. 2007 Oct 3;27(40):10674-84. Halassa MM, Fellin T, Takano H, Dong JH, Haydon PG. Synaptic islands defined by the territory of a single astrocyte. J Neurosci. 2007 Jun 13;27(24):6473-7. D'Ascenzo M, Fellin T, Terunuma M, Revilla-Sanchez R, Meaney DF, Auberson YP, Moss SJ, Haydon PG. mGluR5 stimulates gliotransmission in the nucleus accumbens. Proc Natl Acad Sci U S A. 2007 Feb 6;104(6):1995-2000. Epub 2007 Jan 26. Halassa MM, Fellin T, Haydon PG. The tripartite synapse: roles for gliotransmission in health and disease. Trends Mol Med. 2007 Feb;13(2):54-63. Epub 2007 Jan 4. Fellin T, Gomez-Gonzalo M, Gobbo S, Carmignoto G, Haydon PG. Astrocytic glutamate is not necessary for the generation of epileptiform neuronal activity in hippocampal slices. J Neurosci. 2006 Sep 6;26(36):9312-22. Haydon PG, Carmignoto G. Astrocyte control of synaptic transmission and neurovascular coupling. Physiol Rev. 2006 Jul;86(3):1009-31. Barrett LE, Sul JY, Takano H, Van Bockstaele EJ, Haydon PG, Eberwine JH. Region-directed phototransfection reveals the functional significance of a dendritically synthesized transcription factor. Nat Methods. 2006 Jun;3(6):455-60. Pascual O, Casper KB, Kubera C, Zhang J, Revilla-Sanchez R, Sul JY, Takano H, Moss SJ, McCarthy K, Haydon PG. Astrocytic purinergic signaling coordinates synaptic networks. Science. 2005 Oct 7;310(5745):113-6. Fellin T, Pascual O, Gobbo S, Pozzan T, Haydon PG, Carmignoto G. Neuronal synchrony mediated by astrocytic glutamate through activation of extrasynaptic NMDA receptors. Neuron. 2004 Sep 2;43(5):729-43. Erratum in: Neuron. 2005 Jan 6;45(1):177. Zhang Q, Fukuda M, Van Bockstaele E, Pascual O, Haydon PG. Synaptotagmin IV regulates glial glutamate release. Proc Natl Acad Sci U S A. 2004 Jun 22;101(25):9441-6. Epub 2004 Jun 14. Parpura V, Basarsky TA, Liu F, Jeftinija K, Jeftinija S, Haydon PG. Glutamate-mediated astrocyte-neuron signalling. Nature. 1994 Jun 30;369(6483):744-7. Araque A, Parpura V, Sanzgiri RP, Haydon PG. Tripartite synapses: glia, the unacknowledged partner. Trends Neurosci. 1999 May;22(5):208-15. Haydon PG. GLIA: listening and talking to the synapse. Nat Rev Neurosci. 2001 Mar;2(3):185-93.
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