Microglial Gi-dependent dynamics regulate brain network hyperexcitability

Mario Merlini; Victoria A Rafalski; Keran Ma; Keun-Young Kim; Eric A Bushong; Pamela E Rios Coronado; Zhaoqi Yan; Andrew S Mendiola; Elif G Sozmen; Jae Kyu Ryu; Matthias G Haberl; Matthew Madany; Daniel Naranjo Sampson; Mark A Petersen; Sophia Bardehle; Reshmi Tognatta; Terry Dean Jr; Rosa Meza Acevedo; Belinda Cabriga; Reuben Thomas; Shaun R Coughlin; Mark H Ellisman; Jorge J Palop; Katerina Akassoglou

doi:10.1038/s41593-020-00756-7

Microglial G_i-dependent dynamics regulate brain network hyperexcitability

Nat Neurosci. 2021 Jan;24(1):19-23. doi: 10.1038/s41593-020-00756-7. Epub 2020 Dec 14.

Authors

Mario Merlini^#¹, Victoria A Rafalski^#¹, Keran Ma¹, Keun-Young Kim^{2

3}, Eric A Bushong^{2

3}, Pamela E Rios Coronado¹, Zhaoqi Yan¹, Andrew S Mendiola¹, Elif G Sozmen^{1

4}, Jae Kyu Ryu^{1

4}, Matthias G Haberl^{2

3}, Matthew Madany^{2

3}, Daniel Naranjo Sampson^{2

3}, Mark A Petersen^{1

5}, Sophia Bardehle¹, Reshmi Tognatta¹, Terry Dean Jr^{1

5}, Rosa Meza Acevedo¹, Belinda Cabriga¹, Reuben Thomas¹, Shaun R Coughlin⁶, Mark H Ellisman^{2

3}, Jorge J Palop^{1

4}, Katerina Akassoglou^{7

8}

Affiliations

¹ Gladstone Institutes, San Francisco, CA, USA.
² Department of Neurosciences, University of California, San Diego, La Jolla, CA, USA.
³ National Center for Microscopy and Imaging Research, University of California, San Diego, La Jolla, CA, USA.
⁴ Department of Neurology and Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.
⁵ Department of Pediatrics, University of California, San Francisco, San Francisco, CA, USA.
⁶ Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA, USA.
⁷ Gladstone Institutes, San Francisco, CA, USA. kakassoglou@gladstone.ucsf.edu.
⁸ Department of Neurology and Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA. kakassoglou@gladstone.ucsf.edu.

^# Contributed equally.

Abstract

Microglial surveillance is a key feature of brain physiology and disease. Here, we found that G_i-dependent microglial dynamics prevent neuronal network hyperexcitability. By generating Mg^PTX mice to genetically inhibit G_i in microglia, we show that sustained reduction of microglia brain surveillance and directed process motility induced spontaneous seizures and increased hypersynchrony after physiologically evoked neuronal activity in awake adult mice. Thus, G_i-dependent microglia dynamics may prevent hyperexcitability in neurological diseases.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Calcium Signaling
Cell Movement
Convulsants
Electroencephalography
G-Protein-Coupled Receptor Kinase 1 / physiology*
Immunologic Surveillance
Mice
Microglia / enzymology
Microglia / physiology*
Microglia / ultrastructure
Nerve Net / physiology*
Nervous System Diseases / physiopathology
Nervous System Physiological Phenomena
Pilocarpine
Seizures / physiopathology
Signal Transduction
rho GTP-Binding Proteins / metabolism

Substances

Convulsants
Pilocarpine
G-Protein-Coupled Receptor Kinase 1
Grk1 protein, mouse
rho GTP-Binding Proteins

Abstract

Publication types

MeSH terms

Substances

Grants and funding