Research in our laboratory focuses on the physiology of glial cells and on interactions between glia, neurons and blood vessels in the central nervous system. Glia have traditionally been viewed as passive, housekeeper cells in the brain. This view has been overturned in recent years as studies have demonstrated that glial cells have many essential functions in the CNS and may actively participate in information processing. We are studying several aspects of glial cell function, including i) neuronal activation of glial cells, ii) glial cell modulation of neuronal excitability and synaptic transmission, iii) calcium signaling within and between glial cells, and iv) glial cell regulation of blood flow.
We have demonstrated that astrocytes and Müller cells, the two macroglial cells of the retina, generate both spontaneous and neuron-evoked calcium signals. These calcium signals, in turn, lead to the release of transmitters from glial cells, resulting in the modulation of neuronal excitability. We are currently studying how these glial signals affect information processing in the retina. We are also studying how pathology affects glial calcium signaling.
We have shown that factors released from glial cells regulate blood flow in the retina. Light stimulation or direct activation of glial cells results in the release of arachidonic acid metabolites. Some of these metabolites constrict while others dilate vessels. We are studying how glia to vessel signaling is modulated and the role that glial cells play in controlling blood flow.
(For a comprehensive list of recent publications, refer to PubMed, a service provided by the National Library of Medicine.)
Srienc AI, Biesecker KR, Shimoda AM, Kur J, Newman EA. Ischemia-induced spreading depolarization in the retina. J Cereb Blood Flow Metab. 2016 Jul 7;.
Kornfield TE, Newman EA. Measurement of Retinal Blood Flow Using Fluorescently Labeled Red Blood Cells. Eneuro. 2015 Mar-Apr;2(2).
Newman EA. Glial cell regulation of neuronal activity and blood flow in the retina by release of gliotransmitters. Philos Trans R Soc Lond B Biol Sci. 2015 Jul 5;370(1672).
MacVicar BA, Newman EA. Astrocyte regulation of blood flow in the brain. Cold Spring Harb Perspect Biol. 2015 Mar 27;7(5).
Kornfield TE, Newman EA. Regulation of blood flow in the retinal trilaminar vascular network. J Neurosci. 2014 Aug 20;34(34):11504-13.
Kur J, Newman EA. Purinergic control of vascular tone in the retina. J Physiol. 2014 Feb 1;592(Pt 3):491-504.
Newman EA. Functional hyperemia and mechanisms of neurovascular coupling in the retinal vasculature. J Cereb Blood Flow Metab. 2013 Nov;33(11):1685-95.
Newman MH, Newman EA. MetaNeuron: A Free Neuron Simulation Program for Teaching Cellular Neurophysiology. J Undergrad Neurosci Educ. 2013 Oct 15;12(1):A11-7.
Kur, J., Newman, E.A., and Chan-Ling, T. Cellular and physiological mechanisms underlying blood flow regulation in the retina and choroid in health and disease. Prog. Retin. Eye Res. 2012 Sep;31(5):377-406.
Mishra, A. and Newman, E.A. Aminoguanidine reverses the loss of functional hyperemia in a rat model of diabetic retinopathy. Front.
Srienc AI, Kornfield TE, Mishra A, Burian MA, Newman EA. Assessment of glial function in the in vivo retina. Methods Mol Biol. 2012;814:499-514.
Mishra A, Hamid A, Newman EA. Oxygen modulation of neurovascular coupling in the retina. Proc Natl Acad Sci U S A. 2011 Oct 25;108(43):17827-31. Epub 2011 Oct 17.
Srienc AI, Kurth-Nelson ZL, Newman EA. Imaging retinal blood flow with laser speckle flowmetry. Front Neuroenergetics. 2010 Sep 15;2. pii: 128.
Attwell, D., Buchan, A.M., Charpak, S., Lauritzen, M., MacVicar, B.A. and Newman, E.A. (2010). Glial and neuronal control of brain blood flow. Nature.
Mishra, A. and Newman, E.A. (2010) Inhibition of Inducible Nitric Oxide Synthase Reverses the Loss of Functional Hyperemia in Diabetic Retinopathy. Glia, in press.
Clark, B.D, Kurth-Nelson, Z.L., and Newman, E.A. (2009) Adenosine-evoked hyperpolarization of retinal ganglion cells is mediated by GIRK and SK channel activation. J. Neurosci. 29:11237-11245.
Kurth-Nelson, Z.L., Mishra, A. and Newman, E.A. (2009) Spontaneous glial calcium waves in the retina develop over early adulthood. J. Neurosci. 29:11339-11346.
Metea, M.R. and Newman, E.A. (2006) Glial cells dilate and constrict blood vessels: A mechanism of neurovascular coupling. J. Neurosci, 26:2862-2870.
Newman, E.A. (2005) Calcium increases in retinal glial cells evoked by light-induced neuronal activity. J. Neurosci. 25:5502-5510.
Current Graduate Students:
Tess Kornfield (Neuroscience, University of Minnesota).
Anja Srienc (Neuroscience, University of Minnesota).
Former Graduate Students:
Benjamin Clark (Ph.D. 2009, Neuroscience, University of Minnesota).
Monica Metea (Ph.D. 2006, Neuroscience, University of Minnesota).
Anusha Mishra (Ph.D. 2011, Neuroscience, University of Minnesota).
Zeb Kurth-Nelson (Ph.D. 2009, Neuroscience, University of Minnesota).