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The long-term goals of our work is to understand how neuron-glial interactions modulate brain function and contribute to pathology in neurodegenerative disease. Towards this goal, we study the interactions of oligodendrocyte lineage cells with neurons in the adult cerebral cortex.
Oligodendrocytes are the myelin-forming cells of CNS and their ensheathment of axons is essential for rapid synaptic communication. Oligodendrocyte dysfunction results in a diverse group of pediatric and adult disorders, most notably, X-linked adrenoleukodystrophy and multiple sclerosis. However, our understanding of the functions of oligodendrocytes and their precursors remains in its infancy. We use advanced imaging and cell-specific genetic manipulations to explore dynamic changes in neurons and glial cells in the living adult brain using long-term two-photon in vivo imaging, optogenetics, genetically encoded calcium indicators, and transcriptomics.
Bacmeister CM, Huang R, Osso LA, Thornton MA, Conant L, Chavez A, Poleg-Polsky A, Hughes EG. Motor Learning Drives Dynamic Patterns of Intermittent Myelination on Learning-activated Axons. (2022) In Press, Nature Neuroscience. bioRxiv. https://doi.org/10.1101/2021.10.13.464319
Thornton, MA, Futia GL, Stockton ME, Ozbay BN, Kilborn K, Restrepo D, Gibson EA*, Hughes, EG*. (2022) Characterization of red fluorescent reporters for dual-color in vivo three-photon microscopy. Neurophotonics. 9(3), 031912.
Hughes, E. G. & Stockton, M. E. Premyelinating Oligodendrocytes: Mechanisms Underlying Cell Survival and Integration. (2021) Frontiers in Cell and Developmental Biology 9, 1985.
Bacmeister CM*, Barr HJ*, McClain CR*, Thornton MA, Nettles D, Welle CG, Hughes EG. (2020) Motor Learning Promotes Remyelination via New and Surviving Oligodendrocytes. Nature Neuroscience. 23, 819–831.
Thornton, MA, Hughes, EG. (2020) Neuron-Oligodendroglia Interactions: Activity-Dependent Regulation of Cellular Signaling. Neuroscience Letters. 727, 134916.
Benichoux V, Ferber AT, Hunt SD, Hughes EG, Tollin DJ. (2018) Across species ‘natural ablation’ study reveals the brainstem source for a non-invasive biomarker for binaural hearing. Journal of Neuroscience 1211-18.
Hughes EG*#, Orthmann-Murphy JL*, Langseth AJ, Bergles DE# (2018) Myelin remodeling through experience-dependent oligodendrogenesis in the adult somatosensory cortex. Nature Neuroscience 21, 696–706.
Ozbay BN, Futia GL, Ma M, Bright VM, Gopinath JT, Hughes EG, Restrepo D, Gibson EA. (2018) Three dimensional two-photon brain imaging in freely moving mice using a miniature fiber coupled microscope with active axial-scanning. Scientific Reports 8(1): 8108.
Kim J, Hughes EG, Shetty AS, Arlotta P, Goff LA, Bergles DE, and Brown SP (2017) Changes in the excitability of neocortical neurons in a mouse model of amyotrophic lateral sclerosis are not specific to corticospinal neurons and are modulated by advancing disease. Journal of Neuroscience 37: 9037-9053.
Agarwal A, Wu PH, Hughes EG, Fukaya M, Tischfield MA, Langseth AJ, Wirtz D, Bergles DE (2017) Transient Opening of the Mitochondrial Permeability Transition Pore Induces Microdomain Calcium Transients in Astrocyte Processes. Neuron 93: 587-605.
Hughes EG, Appel B (2016) The cell biology of CNS myelination. Current Opinions in Neurobiology 39: 93-100.
Peng X, Hughes EG, Moscato EH, Parsons TD, Dalmau J, Balice-Gordon RJ. (2015) Cellular plasticity induced by anti-AMPA receptor encephalitis antibodies. Annals of Neurology 77: 381-98.
Hughes EG, Bergles DE. (2014) Hidden progenitors replace microglia in the adult brain. Neuron 82: 253-255.
Hughes EG*, Kang SH*, Fukaya M*, Bergles DE. (2013) Oligodendrocyte progenitors balance growth and self-repulsion to maintain homeostasis in the adult brain. Nature Neuroscience 16: 668–676.
Moscato EH, Jain A, Peng X, Hughes EG, Dalmau J and Balice-Gordon RJ. (2010) Mechanisms underlying autoimmune synaptic encephalitis leading to disorders of memory, behavior and cognition: insights from molecular, cellular and synaptic studies. European Journal of Neuroscience 32: 298-309.
Hughes EG*, Peng X*, Gleichman AJ, Lai M, Zhou L, Lynch DR, Dalmau J, Balice-Gordon RJ. (2010) Cellular and synaptic mechanisms of anti-NMDA receptor encephalitis. Journal of Neuroscience 30: 5866-5875.
Hughes EG, Elmariah SB, Balice-Gordon RJ. (2010) Astrocyte secreted proteins selectively increase hippocampal GABAergic axon length, branching, and synaptogenesis. Molecular Cellular Neuroscience 43: 136-45.
Lancaster E*, Lai M*, Peng X, Hughes E, Constantinescu R, Raizer J, Friedman D, Skeen M, Grisold W, Kimura A, Ohta K, Iizuka T, Graus F, Moss SJ, Balice-Gordon RJ, Dalmau J. (2010) The GABA (B) Receptor is a Novel Autoantigen of Limbic Encephalitis with Prominent Seizures. Lancet Neurology 9: 67-76.
Lai M*, Hughes EG*, Peng X*, Zhou L, Gleichman AJ, Shu H, Mata S, Kremens D, Vitaliani R, Geschwind MD, Bataller L, Kalb RG, Davis R, Graus F, Lynch DR, Balice-Gordon RJ, Dalmau J. (2009) AMPA receptor antibodies in limbic encephalitis alter synaptic receptor location. Annals of Neurology 65: 424-34.
Keene SD*, Greco TM*, Parastatidis I, Lee SH, Hughes EG, Balice-Gordon RJ, Speicher DW and Ischiropoulos H. (2009) Mass spectrometric and computational analysis of cytokine-induced alterations in the astrocyte secretome. Proteomics 3: 768-82.
Dalmau J, Gleichman AJ*, Hughes EG*, Rossi JE, Peng X, Lai M, Deassain S, Rosenfeld MR, Balice-Gordon RJ, Lynch DR. (2008) Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies. Lancet Neurology. 12:1091-8.
Elmariah SB, Hughes EG, Oh EJ, Balice-Gordon RJ. (2008) Neurotrophin signaling among neurons and glia during formation of synapses. In: Beyond the Synapse: cell-cell signaling in synaptic plasticity, R.D. Fields, ed. Cambridge Press. Page 142-152.
Hughes EG, Balice-Gordon RJ. (2007) Extreme Makeover: Synapse Edition. Neuron 53: 779-780.
Kayser MS, McCelland AC, Hughes EG, Dalva MB. (2006) Intra-cellular and trans-synaptic regulation of glutamatergic synaptogenesis by EphB receptors. Journal of Neuroscience 26: 12152-64.
Elmariah SB, Oh EJ, Hughes EG, Balice-Gordon RJ. (2005) Astrocytes regulate inhibitory synapse formation via Trk-mediated modification of postsynaptic GABAA receptors. Journal of Neuroscience 25: 3638-50.
Elmariah SB, Hughes EG, Oh EJ, Balice-Gordon RJ. (2005) Neurotrophin signaling among neurons and glia during formation of tripartite synapses. Neuron Glia Biology 1: 1-11.
Hughes EG, Maguire JL, McMinn MT, Scholz RE, Sutherland ML. (2004) Loss of glial fibrillary acidic protein results in decreased glutamate transport and inhibition of PKA-induced EAAT2 cell surface trafficking. Brain Res. Mol. Brain Res. 124: 114-23.