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3. Reactive astrocyte nomenclature, definitions, and future directions

Author

Escartin, Carole, Galea, Elena, Lakatos, András, O’Callaghan, James P, Petzold, Gabor C, Serrano-Pozo, Alberto, Steinhäuser, Christian, Volterra, Andrea, Carmignoto, Giorgio, Agarwal, Amit, Allen, Nicola J, Araque, Alfonso, Barbeito, Luis, Barzilai, Ari, Bergles, Dwight E, Bonvento, Gilles, Butt, Arthur M, Chen, Wei-Ting, Cohen-Salmon, Martine, Cunningham, Colm, Deneen, Benjamin, De Strooper, Bart, Díaz-Castro, Blanca, Farina, Cinthia, Freeman, Marc, Gallo, Vittorio, Goldman, James E, Goldman, Steven A, Götz, Magdalena, Gutiérrez, Antonia, Haydon, Philip G, Heiland, Dieter H, Hol, Elly M, Holt, Matthew G, Iino, Masamitsu, Kastanenka, Ksenia V, Kettenmann, Helmut, Khakh, Baljit S, Koizumi, Schuichi, Lee, C Justin, Liddelow, Shane A, MacVicar, Brian A, Magistretti, Pierre, Messing, Albee, Mishra, Anusha, Molofsky, Anna V, Murai, Keith K, Norris, Christopher M, Okada, Seiji, Oliet, Stéphane HR, Oliveira, João F, Panatier, Aude, Parpura, Vladimir, Pekna, Marcela, Pekny, Milos, Pellerin, Luc, Perea, Gertrudis, Pérez-Nievas, Beatriz G, Pfrieger, Frank W, Poskanzer, Kira E, Quintana, Francisco J, Ransohoff, Richard M, Riquelme-Perez, Miriam, Robel, Stefanie, Rose, Christine R, Rothstein, Jeffrey D, Rouach, Nathalie, Rowitch, David H, Semyanov, Alexey, Sirko, Swetlana, Sontheimer, Harald, Swanson, Raymond A, Vitorica, Javier, Wanner, Ina-Beate, Wood, Levi B, Wu, Jiaqian, Zheng, Binhai, Zimmer, Eduardo R, Zorec, Robert, Sofroniew, Michael V, and Verkhratsky, Alexei

Subjects
Neurosciences, Brain Disorders, Neurological, Aging, Animals, Astrocytes, Brain, Brain Diseases, Brain Injuries, Humans, Spinal Cord, Spinal Cord Injuries, Psychology, Cognitive Sciences, Neurology & Neurosurgery
Abstract

Reactive astrocytes are astrocytes undergoing morphological, molecular, and functional remodeling in response to injury, disease, or infection of the CNS. Although this remodeling was first described over a century ago, uncertainties and controversies remain regarding the contribution of reactive astrocytes to CNS diseases, repair, and aging. It is also unclear whether fixed categories of reactive astrocytes exist and, if so, how to identify them. We point out the shortcomings of binary divisions of reactive astrocytes into good-vs-bad, neurotoxic-vs-neuroprotective or A1-vs-A2. We advocate, instead, that research on reactive astrocytes include assessment of multiple molecular and functional parameters-preferably in vivo-plus multivariate statistics and determination of impact on pathological hallmarks in relevant models. These guidelines may spur the discovery of astrocyte-based biomarkers as well as astrocyte-targeting therapies that abrogate detrimental actions of reactive astrocytes, potentiate their neuro- and glioprotective actions, and restore or augment their homeostatic, modulatory, and defensive functions.

Published
2021

4. Behaviorally consequential astrocytic regulation of neural circuits

Author

Nagai, Jun, Yu, Xinzhu, Papouin, Thomas, Cheong, Eunji, Freeman, Marc R, Monk, Kelly R, Hastings, Michael H, Haydon, Philip G, Rowitch, David, Shaham, Shai, and Khakh, Baljit S

Subjects
Biological Psychology, Biomedical and Clinical Sciences, Neurosciences, Psychology, 1.1 Normal biological development and functioning, Underpinning research, Generic health relevance, Neurological, Animals, Astrocytes, Caenorhabditis elegans, Drosophila, Humans, Mental Disorders, Mice, Nerve Net, Neurons, Species Specificity, Zebrafish, Danio rerio, Drosophila melanogaster, Mus musculus, astrocyte, behavior, genetic disorders, glia, microcircuit, neuronal circuit, Cognitive Sciences, Neurology & Neurosurgery, Biological psychology
Abstract

Astrocytes are a large and diverse population of morphologically complex cells that exist throughout nervous systems of multiple species. Progress over the last two decades has shown that astrocytes mediate developmental, physiological, and pathological processes. However, a long-standing open question is how astrocytes regulate neural circuits in ways that are behaviorally consequential. In this regard, we summarize recent studies using Caenorhabditis elegans, Drosophila melanogaster, Danio rerio, and Mus musculus. The data reveal diverse astrocyte mechanisms operating in seconds or much longer timescales within neural circuits and shaping multiple behavioral outputs. We also refer to human diseases that have a known primary astrocytic basis. We suggest that including astrocytes in mechanistic, theoretical, and computational studies of neural circuits provides new perspectives to understand behavior, its regulation, and its disease-related manifestations.

Published
2021

6. Integrating Hebbian and homeostatic plasticity: the current state of the field and future research directions

Author

Keck, Tara, Toyoizumi, Taro, Chen, Lu, Doiron, Brent, Feldman, Daniel E, Fox, Kevin, Gerstner, Wulfram, Haydon, Philip G, Hübener, Mark, Lee, Hey-Kyoung, Lisman, John E, Rose, Tobias, Sengpiel, Frank, Stellwagen, David, Stryker, Michael P, Turrigiano, Gina G, and van Rossum, Mark C

Subjects
Animals, Brain, Homeostasis, Humans, Neuronal Plasticity, Hebbian plasticity, homeostatic mechanisms, theoretical modelling, Biological Sciences, Medical and Health Sciences, Evolutionary Biology
Abstract

We summarize here the results presented and subsequent discussion from the meeting on Integrating Hebbian and Homeostatic Plasticity at the Royal Society in April 2016. We first outline the major themes and results presented at the meeting. We next provide a synopsis of the outstanding questions that emerged from the discussion at the end of the meeting and finally suggest potential directions of research that we believe are most promising to develop an understanding of how these two forms of plasticity interact to facilitate functional changes in the brain.This article is part of the themed issue 'Integrating Hebbian and homeostatic plasticity'.

Published
2017

12. Neuronal activity drives pathway-specific depolarization of peripheral astrocyte processes

Author

Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences, Armbruster, Moritz, Naskar, Saptarnab, Garcia, Jacqueline P, Sommer, Mary, Kim, Elliot, Adam, Yoav, Haydon, Philip G, Boyden, Edward S, Cohen, Adam E, Dulla, Chris G, Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences, Armbruster, Moritz, Naskar, Saptarnab, Garcia, Jacqueline P, Sommer, Mary, Kim, Elliot, Adam, Yoav, Haydon, Philip G, Boyden, Edward S, Cohen, Adam E, and Dulla, Chris G

Abstract

Astrocytes are glial cells that interact with neuronal synapses via their distal processes, where they remove glutamate and potassium (K+) from the extracellular space following neuronal activity. Astrocyte clearance of both glutamate and K+ is voltage dependent, but astrocyte membrane potential (Vm) is thought to be largely invariant. As a result, these voltage dependencies have not been considered relevant to astrocyte function. Using genetically encoded voltage indicators to enable the measurement of Vm at peripheral astrocyte processes (PAPs) in mice, we report large, rapid, focal and pathway-specific depolarizations in PAPs during neuronal activity. These activity-dependent astrocyte depolarizations are driven by action potential-mediated presynaptic K+ efflux and electrogenic glutamate transporters. We find that PAP depolarization inhibits astrocyte glutamate clearance during neuronal activity, enhancing neuronal activation by glutamate. This represents a novel class of subcellular astrocyte membrane dynamics and a new form of astrocyte-neuron interaction.

Published
2023

17. Bioengineered functional brain-like cortical tissue

Author

Tang-Schomer, Min D., White, James D., Tien, Lee W., Schmitt, L. Ian, Valentin, Thomas M., Graziano, Daniel J., Hopkins, Amy M., Omenetto, Fiorenzo G., Haydon, Philip G., and Kaplan, David L.

Published
2014

18. 3D bioengineered neural tissue generated from patient-derived iPSCs develops time-dependent phenotypes and transcriptional features of Alzheimer’s disease

Author

Lomoio, Selene, primary, Pandey, Ravi S., additional, Rouleau, Nicolas, additional, Menicacci, Beatrice, additional, Kim, WonHee, additional, Cantley, William L., additional, Haydon, Philip G., additional, Bennett, David A., additional, Young-Pearse, Tracy L., additional, Carter, Gregory W., additional, Kaplan, David L., additional, and Tesco, Giuseppina, additional

Published
2022
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30. List of Contributors

Author

Aoki, Chiye, primary, Ashery, Uri, additional, Barak, Boaz, additional, Bar-On, Dana, additional, Ben-Simon, Yoav, additional, Bielopolski, Noa, additional, Blutstein, Tamara, additional, Cahill, Michael E., additional, Cheyne, Juliette E., additional, Davies, Heather A., additional, De Roo, Mathias, additional, Descarries, Laurent, additional, Dynes, Joseph, additional, Erisir, Alev, additional, Farris, Shannon, additional, Gottfried, Irit, additional, Hara, Yuko, additional, Haydon, Philip G., additional, Heise, Christopher, additional, Horak, Martin, additional, Jones, Kelly A., additional, Kraev, Igor V., additional, Lavi, Ayal, additional, Lohmann, Christian, additional, McEwen, Bruce S., additional, Medvedev, Nikolay, additional, Michaeli, Lirin, additional, Milner, Teresa A., additional, Morrison, John H., additional, Muller, Dominique, additional, Nikonenko, Irina, additional, Parent, Martin, additional, Penzes, Peter, additional, Petralia, Ronald S., additional, Popov, Victor I., additional, Remmers, Christine, additional, Sala, Carlo, additional, Seabold, Gail K., additional, Sesack, Susan R., additional, Shapira, Zehavit, additional, Sheinin, Anton, additional, Steward, Oswald, additional, Stewart, Michael G., additional, Tao-Cheng, Jung-Hwa, additional, VanLeeuwen, Jon-Eric, additional, Verpelli, Chiara, additional, Waters, Elizabeth M., additional, and Woolfrey, Kevin M., additional

Published
2014
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31. Reactive astrocyte nomenclature, definitions, and future directions

Author

Translational Neuroscience, Brain, Cancer, Escartin, Carole, Galea, Elena, Lakatos, András, O’Callaghan, James P., Petzold, Gabor C., Serrano-Pozo, Alberto, Steinhäuser, Christian, Volterra, Andrea, Carmignoto, Giorgio, Agarwal, Amit, Allen, Nicola J., Araque, Alfonso, Barbeito, Luis, Barzilai, Ari, Bergles, Dwight E., Bonvento, Gilles, Butt, Arthur M., Chen, Wei Ting, Cohen-Salmon, Martine, Cunningham, Colm, Deneen, Benjamin, De Strooper, Bart, Díaz-Castro, Blanca, Farina, Cinthia, Freeman, Marc, Gallo, Vittorio, Goldman, James E., Goldman, Steven A., Götz, Magdalena, Gutiérrez, Antonia, Haydon, Philip G., Heiland, Dieter H., Hol, Elly M., Holt, Matthew G., Iino, Masamitsu, Kastanenka, Ksenia V., Kettenmann, Helmut, Khakh, Baljit S., Koizumi, Schuichi, Lee, C. Justin, Liddelow, Shane A., MacVicar, Brian A., Magistretti, Pierre, Messing, Albee, Mishra, Anusha, Molofsky, Anna V., Murai, Keith K., Norris, Christopher M., Okada, Seiji, Oliet, Stéphane H.R., Oliveira, João F., Panatier, Aude, Parpura, Vladimir, Pekna, Marcela, Pekny, Milos, Pellerin, Luc, Perea, Gertrudis, Pérez-Nievas, Beatriz G., Pfrieger, Frank W., Poskanzer, Kira E., Quintana, Francisco J., Ransohoff, Richard M., Riquelme-Perez, Miriam, Robel, Stefanie, Rose, Christine R., Rothstein, Jeffrey D., Rouach, Nathalie, Rowitch, David H., Semyanov, Alexey, Sirko, Swetlana, Sontheimer, Harald, Swanson, Raymond A., Vitorica, Javier, Wanner, Ina Beate, Wood, Levi B., Wu, Jiaqian, Zheng, Binhai, Zimmer, Eduardo R., Zorec, Robert, Sofroniew, Michael V., Verkhratsky, Alexei, Translational Neuroscience, Brain, Cancer, Escartin, Carole, Galea, Elena, Lakatos, András, O’Callaghan, James P., Petzold, Gabor C., Serrano-Pozo, Alberto, Steinhäuser, Christian, Volterra, Andrea, Carmignoto, Giorgio, Agarwal, Amit, Allen, Nicola J., Araque, Alfonso, Barbeito, Luis, Barzilai, Ari, Bergles, Dwight E., Bonvento, Gilles, Butt, Arthur M., Chen, Wei Ting, Cohen-Salmon, Martine, Cunningham, Colm, Deneen, Benjamin, De Strooper, Bart, Díaz-Castro, Blanca, Farina, Cinthia, Freeman, Marc, Gallo, Vittorio, Goldman, James E., Goldman, Steven A., Götz, Magdalena, Gutiérrez, Antonia, Haydon, Philip G., Heiland, Dieter H., Hol, Elly M., Holt, Matthew G., Iino, Masamitsu, Kastanenka, Ksenia V., Kettenmann, Helmut, Khakh, Baljit S., Koizumi, Schuichi, Lee, C. Justin, Liddelow, Shane A., MacVicar, Brian A., Magistretti, Pierre, Messing, Albee, Mishra, Anusha, Molofsky, Anna V., Murai, Keith K., Norris, Christopher M., Okada, Seiji, Oliet, Stéphane H.R., Oliveira, João F., Panatier, Aude, Parpura, Vladimir, Pekna, Marcela, Pekny, Milos, Pellerin, Luc, Perea, Gertrudis, Pérez-Nievas, Beatriz G., Pfrieger, Frank W., Poskanzer, Kira E., Quintana, Francisco J., Ransohoff, Richard M., Riquelme-Perez, Miriam, Robel, Stefanie, Rose, Christine R., Rothstein, Jeffrey D., Rouach, Nathalie, Rowitch, David H., Semyanov, Alexey, Sirko, Swetlana, Sontheimer, Harald, Swanson, Raymond A., Vitorica, Javier, Wanner, Ina Beate, Wood, Levi B., Wu, Jiaqian, Zheng, Binhai, Zimmer, Eduardo R., Zorec, Robert, Sofroniew, Michael V., and Verkhratsky, Alexei

Published
2021

35. Astrocyte control of synaptic transmission and neurovascular coupling

Author

Haydon, Philip G. and Carmignoto, Giorgio

Subjects
Neurovascular diseases -- Research, Astrocytes -- Research, Biological sciences, Health, Research
Abstract

I. Introduction II. Astrocytic Calcium Signaling: The Biochemical Basis of Glial Excitability III. Neuron-to-Astrocyte Signaling in the Control of Cerebral Circulation IV. Neuronal Activity-Dependent Calcium Elevations in Astrocyte Endfeet V. [...]

Published
2006

36. Live imaging of regenerating lamprey spinal axons

Author

Zhang, Guixin, Jin, Li-Qing, Sul, Jai-Yoon, Haydon, Philip G., and Selzer, Michael E.

Subjects
Cytoplasmic filaments, Regeneration (Biology), Spinal cord injuries -- Care and treatment, Psychology and mental health, Care and treatment
Abstract

Background. The sea lamprey has been used as a model for the study of axonal regeneration after spinal cord injury. Although the growing tips of developing axons in lamprey have [...]

Published
2005

41. List of Contributors

Author

Albers, R.Wayne, primary, Anderson, George M., additional, Art, Jonathan, additional, Asatryan, Aram, additional, Baghdoyan, Helen A., additional, Bazan, Nicolas G., additional, Belayev, Ludmila S., additional, Benjamins, Joyce A., additional, Bertram, Lars, additional, Bibb, James A., additional, Blandina, Patrizio, additional, Bongarzone, Ernesto R., additional, Brady, Scott T., additional, Carson, Monica J., additional, Catterall, William A., additional, Chiang, Po-Min, additional, Collinge, John W., additional, Coyle, Joseph T., additional, Currier, Dianne, additional, Dienel, Gerald A., additional, DeLong, Mahlon R., additional, De Vivo, Darryl C., additional, DiMauro, Salvatore, additional, Dingledine, Raymond, additional, Duman, Ronald S., additional, Eady, Tiffany N., additional, Eberwine, James, additional, Eipper, Betty A., additional, Ertel, Monica, additional, Farrer, Robert G., additional, Fisher, Stephen K., additional, Friedman, Wilma, additional, Fuss, Babette, additional, Gillespie, Peter G., additional, Givogri, Maria I., additional, Gnegy, Margaret E., additional, Goedert, Michel, additional, Gould, Georgianna G., additional, Haas, Helmut L., additional, Halabi, Anasheh, additional, Hall, Alison K., additional, Hassel, Bjørnar, additional, Haydon, Philip G., additional, Heacock, Anne, additional, Hensler, Julie G., additional, Hille, Bertil, additional, Holz, Ronald W., additional, Horstkorte, Rüdiger, additional, Hough, Lindsay B., additional, Inquimbert, Perrine, additional, Jones, Daniel L., additional, Kartje, Gwendolyn L., additional, Kirkpatrick, Laura L., additional, Koliatsos, Vassilis, additional, Konopaske, Glenn T., additional, Krey, Jocelyn F., additional, La Spada, Albert R., additional, Lau, Lit-Fui, additional, Leurs, Rob, additional, Li, Guo-Dong, additional, Li, Tong, additional, Lill, Christine, additional, Lovatt, Ditte, additional, Lu, Youming, additional, Lydic, Ralph, additional, Macklin, Wendy B., additional, Mains, Richard E., additional, Manji, Husseini K., additional, Mann, J.John, additional, Martin, Lee J., additional, Mattson, Mark P., additional, McEwen, Bruce S., additional, McKenna, Mary C., additional, McNamara, James O., additional, Miller, Robert H., additional, Morfini, Gerardo, additional, Munger, Steven D., additional, Murphy, Eric J., additional, Nestler, Eric J., additional, O'Brien, Charles P., additional, Olsen, Richard W., additional, Pascual, Juan M., additional, Petasis, Nicos A., additional, Pigino, Gustavo, additional, Pittenger, Christopher, additional, Plattner, Florian, additional, Popko, Brian K., additional, Price, Donald L., additional, Quiroz, Jorge A., additional, Rasband, Matthew N., additional, Savonenko, Alena, additional, Schochet, Terri, additional, Scholz, Joachim, additional, Schousboe, Arne, additional, Schwab, Martin E., additional, Seyfried, Thomas N., additional, Siegel, George J., additional, Soliven, Betty, additional, Song, Yuyu, additional, Sonnewald, Ursula, additional, Spillantini, Maria Grazia, additional, Stark, David T., additional, Staugaitis, Susan M., additional, Stenoien, David L., additional, Tai, Leon, additional, Tanzi, Rudolph E., additional, Trapp, Bruce D., additional, Tsien, Joe Z., additional, Waagepetersen, Helle S., additional, Wadsworth, Jonathan, additional, Wensel, Theodore G., additional, Wichmann, Thomas, additional, Wolf, Marina E., additional, Wong, Philip C., additional, Wonnacott, Susan, additional, Xie, Zijian, additional, Yudkoff, Marc, additional, Zachariou, Venetia, additional, and Zahra, Raheeb L., additional

Published
2012
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45. Micropatterned substrates: approach to probing intercellular communication pathways

Author

Takano, Hajime, Sul, Jai-Yoon, Mazzanti, Mary L., Doyle, Robert T., Haydon, Philip G., and Porter, Marc D.

Subjects
Chemistry, Analytic -- Research, Cells -- Physiological aspects, Cells -- Growth, Central nervous system -- Physiological aspects, Polymers -- Composition, Dielectric films -- Physiological aspects, Thin films, Cell adhesion -- Physiological aspects, Company growth, Chemistry
Abstract

Intercellular signaling is critical for the normal development and physiology of the central nervous system (CNS). To study such signaling, it is vital to control where and when the cells make contact with one another. It is also important to determine whether the process used for cell localization has an impact on signaling. This paper describes a technique that controls the location for cell growth in vitro and demonstrates that the technique has minimal (if any) impact on intercellular signaling. By using photolithographic methods, poly(dimethylsiloxane) molds were fabricated to function as templates for micrometer-level patterning of a nonadhesive agar (agarose) onto glass coverslips coated with a cell adhesive film (poly(L-lysine)). This process yields a surface composed of well-defined adhesive and nonadhesive microdomains. When endothelia or astrocytes are plated onto these substrates, confluent domains of endothelia or astrocytes grow on the poly(L-lysine) domains. Cocultures of astrocytes and neurons can also successfully be used to form interwoven networks on the adhesive domains. Moreover, studies of calcium signaling revealed that astrocytes grown on such patterns retain their native physiological activity. This conclusion is based on the observed propagation rate for calcium waves within individual astrocyte domains and across neighboring, but spatially disconnected, astrocyte domains. The potential to apply these micropatterned substrates as platforms for interrogating communication pathways in key components of the CNS is discussed.

Published
2002

47. Glial cells in (patho)physiology

Author

Parpura, Vladimir, Heneka, Michael T., Montana, Vedrana, Oliet, Stéphane H. R., Schousboe, Arne, Haydon, Philip G., Stout, Randy F., Spray, David C., Reichenbach, Andreas, Pannicke, Thomas, Pekny, Milos, Pekna, Marcela, Zorec, Robert, and Verkhratsky, Alexei

Published
2012
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50. Dynamic signaling between astrocytes and neurons

Author

Araque, Alfonso, Carmignoto, Giorgio, and Haydon, Philip G.

Subjects
Physiology -- Research, Neurons -- Physiological aspects, Astrocytes -- Physiological aspects, Cellular signal transduction -- Research, Neuroglia -- Physiological aspects, Schwann cells -- Physiological aspects, Synapses -- Physiological aspects, Calcium in the body -- Research, Glutamate -- Physiological aspects, Cell interaction -- Research, Biological sciences
Abstract

Dynamic signaling between neurons and astrocytes, a subgroup of clia in the central nervous system, dynamic signaling elements, is discussed with the goal of focusing attention on one of the most recently identified roles of glial cells, the role as integrators and modulators of neuronal activity and synaptic transmission. A look at properties of perisynaptic Schwann cells is included.

Published
2001

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