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Researcher Profile - Lorna Role |
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| First Name: | Lorna | | Last Name: | Role | | Title: | Professor | | Advanced Degrees: | Ph.D. | | Affiliation: | Columbia University P & S | | Department: | Neurobiology | | City: | New York | | State/Province: | NY | Country/Territory: | U.S.A. | | Phone: | 212 305 8117 | | Fax: | 212 795 0700 | | Email Address: |  |
Disclosure:
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Member reports no financial or other potential conflicts of interest. [Last Modified: 14 February 2007]
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View all comments by Lorna Role
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Schizophrenia, Drug abuse
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Molecular and Cell biology, Neuroanatomy/Systems Neuroscience, Neurotransmission, Electrophysiology, Signal transduction, Animal models, Cell biology, Neurodevelopment, Pharmacology, GABAergic transmission, Glutamatergic transmission
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Central cholinergic systems provide important modulatory control on circuit excitability and have been strongly implicated in neuropsychiatric disorders of attention, volition, memory and mood (eg Schizophrenia, Alzheimer’s).
The Role Laboratory studies the generation, plasticity, and maintenance of cholinergic and cholinoceptive synapses in the mammalian brain. We are particularly interested in the role of cholinoceptive pathways in motivational aspects of behavior and natural reward as well as in nicotine addiction. Recent work examines the role of molecular signals that are products of the neuregulin-1 gene in the regulation of neuronal nicotinic acetylcholine receptors and tests the hypothesis that Neuregulin-signaling is important to basic aspects of synaptic homeostasis.
We find that Neuregulin-1-signaling is essential to the maintenance of normal cholinergic circuits and have demonstrated that the Type III neuregulin-1-expressing neurons require bi-directional neuregulin signaling to survive. Current work, in collaboration with the Dr Talmage’s laboratory, employs molecular and biochemical approaches to determine the specific signaling cascades and target genes that are affected by interactions of neuregulin-1 with its receptor (erbB), in pre- and postsynaptic neurons as well as glia. The role of neuregulin-1 signaling at cholinoceptive sites and in the maintenance of synaptic function is also being studied with electrophysiological and behavioral analyses of mice genetically altered in the levels of expression of Type III neuregulin-1 protein. The neuregulin-1 gene has recently been confirmed as a potential susceptibility locus for schizophrenia and 90% of schizophrenia patients smoke. We hope that our current and future work will provide insight into the role of Neuregulin 1 and nicotinic signaling at synapses and circuits whose dysfunction may underlie neuropsychiatric disorders and addiction mechanisms.
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McGehee, D., Heath, M., Gelber, S. and L.W. Role (1995) Nicotine enhancement of fast excitatory synaptic transmission in CNS by presynaptic receptors Science 269: 1692-1697
Ramirez-Latorre, J., Yu, C., Qu, X., Perin, F., Karlin, A. and L. Role (1996) Functional contributions of 5 subunit to neuronal acetylcholine receptor channels. Nature 380:347-351
Yang, X., Kuo, Y., Devay, P., Yu, C., and Role, L. (1998) A cysteine-rich isoform of neuregulin controls nicotinic receptor expression in neurons during synaptogenesis. Neuron 20: 255-270.
Wolpowitz, D., Mason, T.B.A., Dietrich, P., Mendelsohn, M., Talmage, D.A. and Role, L.W. (2000) Cysteine-rich domain isoforms of the Neuregulin-1 gene are required for maintenance of peripheral synapses. Neuron 25:79-91.
Bao, J., Wolpowitz, D., Role, L., and Talmage, D.A. (2003). Back-Signaling by the Neuregulin-1 intracellular Domain (J. Cell Biology 161:1133-1141)
Michailov GV, Sereda MW, Brinkmann BG, Fischer TM, Haug B, Birchmeier C, Role L, Lai C, Schwab MH, Nave KA. (2004). Axonal neuregulin-1 regulates myelin sheath thickness. Science 304(5671):700-3.
Taveggia, C., Zanazzi, G., Petrylak, A., Yano, H, Rosenbluth., J.., Einheber., Esper, RM., Loeb J., Shrager, P., Chao MV., Falls., D., Role, L. and JL Salzer (2005) Neuregulin-1 Type III Determines the Ensheathment Fate of Axons. Neuron.;47(5):681-694.
Jo YH, Wiedl, D and Role, LW (2005) Cholinergic modulation of appetite related synapses in mouse lateral hypothalamic slice J Neuroscience: 25(48):11133-44.
Jo YH, Chua S., Talmage D.A. and Role LW (2005) Integration of Endocannabinoid and Leptin Signaling in an Appetite related Neural Circuit. Neuron: 48: 1055-1066.
Lopez Bendito, G., Cautinat, A., Sanchez, J.A., Bielle, Flames, N., Garratt, A. N., Talmage, DA, Role, L.W.., Charnay, P. Marin, O. & Garel, S. (2006) Tangential Migration Controls Axon Guidance: A Role for Neuregulin 1 in thalamocortical axon navigation Cell : 125: 127-142
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