Paulo Kofuji, PhD
Associate Professor, Department of Neuroscience
Structure and Function of Potassium Channels in Glia
Ion channels in glial cells
A major effort in our laboratory aims to elucidate the role of inwardly rectifying potassium channels for glial cell function. Glial buffering of the extracellular potassium concentration in the retina has been elegantly demonstrated using electrophysiological methods. Inwardly rectifying potassium channels in these glial cells are spatially localized to optimally perform this function. Research in our laboratory has established the essential role of the glial Kir4.1 channel for the buffering of extracellular potassium concentration. More recently we have been investigating the role of accessory proteins for the modulation and subcellular localization of Kir4.1 channels in Müller cells. We have identified a potential macromolecular complex (Aquaporin-4, Kir4.1 and alpha syntrophin) that hold this cluster together. We are now expanding our research to glial cells in the brain and peripheral nervous system.
Another research program in our lab is to elucidate the structure and function of the non-image-forming vision. In mammals, photic information is exclusively processed by the retina and reaches the brain through the optic nerve. The eyes are equipped with at least two functionally and anatomically distinct light-detecting streams, the classic image-forming stream involving rods and cones and the non-image forming stream. The non–image-forming photoreceptive stream entrains the circadian timing system and regulates pineal melatonin secretion and pupillary constriction. A small subpopulation of ganglion cells in the mammalian retina expresses the opsin-family photopigment melanopsin (Opn4). These ganglion cells are intrinsically photosensitive (ipRGC) and play a crucial role in “non-image forming” visual responses such as circadian photoentrainment. We have identified subpopulations of ipRGCs with distinct anatomical and functional properties using electrophysiological and genetics methods. We are now studying the role of ipRGCs in a variety of light-evoked behaviors that support organismal responses to environmental light.
Corkrum, M, Covelo, A, Lines, J, Bellocchio, L, Pisansky, M, Loke, K, Quintana, R, Rothwell, PE, Lujan, R, Marsicano, G, Martin, ED, Thomas, MJ, Kofuji, P & Araque, A 2020, 'Dopamine-Evoked Synaptic Regulation in the Nucleus Accumbens Requires Astrocyte Activity', Neuron. https://doi.org/10.1016/j.neuron.2019.12.026
Corkrum, M, Rothwell, PE, Thomas, MJ, Kofuji, P & Araque, A 2019, ‘Opioid-Mediated Astrocyte-Neuron Signaling in the Nucleus Accumbens’ Cells, vol. 8, no. 6. https://doi.org/10.3390/cells8060586
Engeland, WC, Massman, L, Miller, L, Leng, S, Pignatti, E, Pantano, L, Carlone, DL, Kofuji, P & Breault, DT 2019, 'Sex Differences in Adrenal Bmal1 Deletion-Induced Augmentation of Glucocorticoid Responses to Stress and ACTH in Mice', Endocrinology, vol. 160, no. 10, pp. 2215-2229. https://doi.org/10.1210/en.2019-00357
Durkee, CA, Covelo, A, Lines, J, Kofuji, P, Aguilar, J & Araque, A 2019, 'G i/o protein-coupled receptors inhibit neurons but activate astrocytes and stimulate gliotransmission' Glia, vol. 67, no. 6, pp. 1076-1093. https://doi.org/10.1002/glia.23589
Engeland, WC, Massman, L, Mishra, S, Yoder, JM, Leng, S, Pignatti, E, Piper, ME, Carlone, DL, Breault, DT & Kofuji, P 2018, 'The Adrenal Clock Prevents Aberrant Light-Induced Alterations in Circadian Glucocorticoid Rhythms' Endocrinology, vol. 159, no. 12, pp. 3950-3964. https://doi.org/10.1210/en.2018-00769
Kofuji, P, Mure, LS, Massman, LJ, Purrier, N, Panda, S & Engeland, WC 2016, 'Intrinsically photosensitive retinal ganglion cells (ipRGCs) are necessary for light entrainment of peripheral clocks' PloS one, vol. 11, no. 12, e0168651.. https://doi.org/10.1371/journal.pone.0168651
Biesecker, KR, Srienc, AI, Shimoda, AM, Agarwal, A, Bergles, DE, Kofuji, P & Newman, EA 2016, 'Cell calcium signaling mediates capillary regulation of blood flow in the Retina' Journal of Neuroscience, vol. 36, no. 36, pp. 9435-9445. https://doi.org/10.1523/JNEUROSCI.1782-16.2016
Purrier, N, Engeland, WC & Kofuji, P 2014, 'Mice deficient of glutamatergic signaling from intrinsically photosensitive retinal ganglion cells exhibit abnormal circadian photoentrainment' PLoS One, vol. 9, no. 10, e111449. https://doi.org/10.1371/journal.pone.0111449
Chew, KS, Schmidt, TM, Rupp, AC, Kofuji, P & Trimarchi, JM 2014, 'Loss of Gq/11 genes does not abolish melanopsin phototransduction' PLoS One, vol. 9, no. 5, e98356. https://doi.org/10.1371/journal.pone.0098356
Schmidt, TM, Alam, NM, Chen, S, Kofuji, P, Li, W, Prusky, GT & Hattar, S 2014, 'A Role for Melanopsin in Alpha Retinal Ganglion Cells and Contrast Detection' Neuron, vol. 82, no. 4, pp. 781-788. https://doi.org/10.1016/j.neuron.2014.03.022
NSC 5203: Neuroscience of Vision (Fall semester); NSC 5551: Itasca Cell and Molecular Neurobiology Laboratory (Summer semester); NSC 5561: Systems Neuroscience (Fall semester); NSC 6111: Human Neuroscience (Fall semester).