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MicroCONtACT SIGNED

Microglial control of neuronal activity in the healthy and the injured brain

Total Cost €

EC-Contrib. €

Partnership

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MicroCONtACT project word cloud

Explore the words cloud of the MicroCONtACT project. It provides you a very rough idea of what is the project "MicroCONtACT" about.

neurophysiological manipulation nanoscale neuron microglial acute difficulties previously depletion pathophysiological first unpublished depolarization had mechanisms vitro tools networks time shape limit excitability super manipulating preliminary context imaging suggest combined interactions photon calcium immune data inflammation shaping fast csf1r optogenetic resolution manipulate network death remained unclear injury microglia chemogenic cells injured unexplored combine occurs eeg molecular diseases reveal contributor selectively spreading disrupt brain constantly microscopy underlying healthy mediated intracranial actions selective vivo monitor survival signaling controversial regulators neuronal excitotoxicity

Project "MicroCONtACT" data sheet

The following table provides information about the project.

Coordinator	INSTITUTE OF EXPERIMENTAL MEDICINE - HUNGARIAN ACADEMY OF SCIENCES Organization address address: Szigony utca 43 city: Budapest postcode: 1083 website: www.koki.hu contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.
Coordinator Country	Hungary [HU]
Total cost	2˙000˙000 €
EC max contribution	2˙000˙000 € (100%)
Programme	1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
Code Call	ERC-2016-COG
Funding Scheme	ERC-COG
Starting year	2017
Duration (year-month-day)	from 2017-04-01 to 2022-03-31

Partnership

Take a look of project's partnership.

#	participants	country	role	EC contrib. [€]
1	INSTITUTE OF EXPERIMENTAL MEDICINE - HUNGARIAN ACADEMY OF SCIENCES INSTITUTE OF EXPERIMENTAL MEDICINE - HUNGARIAN ACADEMY OF SCIENCES Organization address address: Szigony utca 43 city: Budapest postcode: 1083 website: www.koki.hu contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.	HU (Budapest)	coordinator	2˙000˙000.00

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Project objective

Microglia are the main immune cells of the brain, but their role in brain injury is highly controversial due to the difficulties in selectively manipulating and imaging microglial actions in real time. Specifically, it is unclear whether microglia control neuronal survival after injury via shaping the activity of complex neuronal networks in vivo. To this end, we have combined fast in vivo two-photon imaging of neuronal calcium responses with selective microglial manipulation for the first time. Our data suggest that microglia constantly monitor and control neuronal network activity and these actions are essential to limit excitotoxicity and neuronal death after acute brain injury. We also identify microglia as key regulators of spreading depolarization in vivo. However, the underlying mechanisms remained unexplored. Here, I propose that microglia control neuronal excitability and based on preliminary data I set out to investigate how this occurs. We will combine selective, CSF1R-mediated microglia depletion with advanced neurophysiological methods such as in vivo calcium imaging and intracranial EEG for the first time, to reveal how microglia shape activity of complex neuronal networks in the healthy and the injured brain. Then, we will study microglia-neuron interactions from the network level to nanoscale level using in vivo two-photon imaging and super-resolution microscopy. We will apply novel chemogenic and optogenetic approaches to manipulate microglia in real time, assess their role in neuronal activity changes and investigate the molecular mechanisms in vitro and in vivo. Our unpublished data also suggest that inflammation – a key contributor to brain diseases – could disrupt microglia-neuron signaling and we set out to investigate the underlying mechanisms. By using state-of the-art research tools that had not been applied previously in this context, our studies are likely to reveal novel pathophysiological mechanisms relevant for common brain diseases.

Publications

List of publications.
year	authors and title	journal	last update
2020	DÃ¡niel P Varga, Ãkos MenyhÃ¡rt, BalÃ¡zs PÃ³sfai, Eszter CsÃ¡szÃ¡r, Nikolett LÃ©nÃ¡rt, Csaba CserÃ©p, Barbara Orsolits, Bernadett Martinecz, TamÃ¡s SzlepÃ¡k, Ferenc Bari, Eszter Farkas, ÃdÃ¡m DÃ©nes Microglia alter the threshold of spreading depolarization and related potassium uptake in the mouse brain published pages: 0271678X1990009, ISSN: 0271-678X, DOI: 10.1177/0271678x19900097	Journal of Cerebral Blood Flow & Metabolism	2020-04-07
2020	Csaba CserÃ©p, BalÃ¡zs PÃ³sfai, Nikolett LÃ©nÃ¡rt, Rebeka Fekete, ZsÃ³fia I. LÃ¡szlÃ³, Zsolt Lele, Barbara Orsolits, GÃ¡bor MolnÃ¡r, Steffanie Heindl, Anett D. Schwarcz, Katinka UjvÃ¡ri, Zsuzsanna KÃ¶rnyei, Krisztina TÃ³th, Eszter Szabadits, BeÃ¡ta SperlÃ¡gh, MÃ¡ria Baranyi, LÃ¡szlÃ³ Csiba, Tibor HortobÃ¡gyi, ZsÃ³fia MaglÃ³czky, Bernadett Martinecz, GÃ¡bor SzabÃ³, Ferenc ErdÃ©lyi, RÃ³bert SzipÅ‘cs Microglia monitor and protect neuronal function through specialized somatic purinergic junctions published pages: 528-537, ISSN: 0036-8075, DOI: 10.1126/science.aax6752	Science 367/6477	2020-04-07
2019	Csaba CserÃ©p, BalÃ¡zs PÃ³sfai, Barbara Orsolits, GÃ¡bor MolnÃ¡r, Steffanie Heindl, Nikolett LÃ©nÃ¡rt, Rebeka Fekete, ZsÃ³fia I. LÃ¡szlÃ³, Zsolt Lele, Anett D. Schwarcz, Katinka UjvÃ¡ri, LÃ¡szlÃ³ Csiba, Tibor HortobÃ¡gyi, ZsÃ³fia MaglÃ³czky, Bernadett Martinecz, GÃ¡bor SzabÃ³, Ferenc ErdÃ©lyi, RÃ³bert SzipÅ‘cs, Benno Gesierich, Marco Duering, IstvÃ¡n Katona, Arthur Liesz, GÃ¡bor TamÃ¡s, ÃdÃ¡m DÃ© Microglia monitor and protect neuronal function via specialized somatic purinergic junctions published pages: , ISSN: , DOI: 10.1101/606079	bioRxiv.org - the preprint server for Biology	2019-10-15
2019	Zsuzsanna Helyes, ValÃ©ria TÃ©kus, Nikolett Szentes, Krisztina PohÃ³czky, BÃ¡lint Botz, TamÃ¡s Kiss, Ãgnes KemÃ©ny, Zsuzsanna KÃ¶rnyei, Krisztina TÃ³th, Nikolett LÃ©nÃ¡rt, Hajnalka ÃbrahÃ¡m, Emmanuel Pinteaux, Sheila Francis, Serena Sensi, ÃdÃ¡m DÃ©nes, Andreas Goebel Transfer of complex regional pain syndrome to mice via human autoantibodies is mediated by interleukin-1â€“induced mechanisms published pages: 13067-13076, ISSN: 0027-8424, DOI: 10.1073/pnas.1820168116	Proceedings of the National Academy of Sciences 116/26	2019-10-07
2019	Lilla Lenart, Dora B. Balogh, Nikolett Lenart, Adrienn Barczi, Adam Hosszu, Tamas Farkas, Judit Hodrea, Attila J. Szabo, Krisztian Szigeti, Adam Denes, Andrea Fekete Novel therapeutic potential of angiotensin receptor 1 blockade in a rat model of diabetes-associated depression parallels altered BDNF signalling published pages: 1501-1513, ISSN: 0012-186X, DOI: 10.1007/s00125-019-4888-z	Diabetologia 62/8	2019-10-07
2019	Kelly L. Singel, Kassondra S. Grzankowski, A. N. M. Nazmul H. Khan, Melissa J. Grimm, Anthony C. Dâ€™Auria, Kayla Morrell, Kevin H. Eng, Bonnie Hylander, Paul C. Mayor, Tiffany R. Emmons, Nikolett LÃ©nÃ¡rt, Rebeka Fekete, Zsuzsanna KÃ¶rnyei, Uma Muthukrishnan, Jonathan D. Gilthorpe, Constantin F. Urban, Kiyoshi Itagaki, Carl J. Hauser, Cynthia Leifer, Kirsten B. Moysich, Kunle Odunsi, ÃdÃ¡m DÃ©ne Mitochondrial DNA in the tumour microenvironment activates neutrophils and is associated with worse outcomes in patients with advanced epithelial ovarian cancer published pages: 207-217, ISSN: 0007-0920, DOI: 10.1038/s41416-018-0339-8	British Journal of Cancer 120/2	2019-10-07
2018	Gergely KovÃ¡cs, Zsuzsanna KÃ¶rnyei, Krisztina TÃ³th, MÃ¡ria Baranyi, JÃ¡nos Brunner, MÃ¡tÃ© Neubrandt, ÃdÃ¡m DÃ©nes, BeÃ¡ta SperlÃ¡gh Modulation of P2X7 purinergic receptor activity by extracellular Zn2+ in cultured mouse hippocampal astroglia published pages: 1-13, ISSN: 0143-4160, DOI: 10.1016/j.ceca.2018.07.010	Cell Calcium 75	2019-10-07
2018	CserÃ©p, Csaba; PÃ³sfai, BalÃ¡zs; Schwarcz, Anett DÃ³ra; DÃ©nes, ÃdÃ¡m Mitochondrial Ultrastructure Is Coupled to Synaptic Performance at Axonal Release Sites published pages: , ISSN: 2373-2822, DOI: 10.1101/216093	eNeuro 1	2019-04-18
2018	Rebeka Fekete, Csaba CserÃ©p, Nikolett LÃ©nÃ¡rt, Krisztina TÃ³th, Barbara Orsolits, Bernadett Martinecz, ElÅ‘d MÃ©hes, BÃ¡lint SzabÃ³, ValÃ©ria NÃ©meth, BalÃ¡zs GÃ¶nci, BeÃ¡ta SperlÃ¡gh, Zsolt BoldogkÅ‘i, Ãgnes Kittel, MÃ¡ria Baranyi, SzilamÃ©r Ferenczi, Krisztina KovÃ¡cs, Gergely Szalay, BalÃ¡zs RÃ³zsa, Connor Webb, Gabor G. Kovacs, Tibor HortobÃ¡gyi, Brian L. West, Zsuzsanna KÃ¶rnyei, ÃdÃ¡m DÃ©nes Microglia control the spread of neurotropic virus infection via P2Y12 signalling and recruit monocytes through P2Y12-independent mechanisms published pages: 461-482, ISSN: 0001-6322, DOI: 10.1007/s00401-018-1885-0	Acta Neuropathologica 136/3	2019-04-18
2018	VirÃ¡g T. TakÃ¡cs, Csaba CserÃ©p, DÃ¡niel Schlingloff, BalÃ¡zs PÃ³sfai, AndrÃ¡s SzÅ‘nyi, Katalin E. Sos, Zsuzsanna KÃ¶rnyei, ÃdÃ¡m DÃ©nes, Attila I. GulyÃ¡s, TamÃ¡s F. Freund, GÃ¡bor Nyiri Co-transmission of acetylcholine and GABA regulates hippocampal states published pages: , ISSN: 2041-1723, DOI: 10.1038/s41467-018-05136-1	Nature Communications 9/1	2019-04-18
2018	BalÃ¡zs PÃ³sfai, Csaba CserÃ©p, Barbara Orsolits, ÃdÃ¡m DÃ©nes New Insights into Microgliaâ€“Neuron Interactions: A Neuronâ€™s Perspective published pages: , ISSN: 0306-4522, DOI: 10.1016/j.neuroscience.2018.04.046	Neuroscience	2019-04-18

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