Balázs Pósfai1, Csaba Cserép1, Katinka Ujvári1, Anett Dóra Schwarcz1, Rebeka Fekete1, Nikolett Lénárt1, Ádám Dénes1
1 Laboratory of Neuroimmunology, Institute of Experimental Medicine, Budapest
Introduction: Microglia are the main immune-competent cells of the central nervous system and their contribution to brain development and neurological diseases has been widely studied. Recent evidences suggest that normal microglial activity is necessary for proper neuronal and network functions even under physiological conditions.
Aims: We aimed to investigate main sites of communication between microglia and neurons, through which microglia might be able to sense and shape neuronal activity. To this end, microglia-neuron interactions were studied in response to physiological neuronal activity and brain injury induced by acute ischemic stroke.
Method: We combined in vivo two-photon imaging with confocal laser scanning- and electron microscopy, as well as electron tomography. Neuronal activity was induced using a chemogenetic approach; ischemic stroke was evoked by occlusion of the medial cerebral artery. Control and ischemic human brain tissues have also been studied to further confirm the relevance of our findings.
Results: We have identified a novel site of interaction between microglial processes and neuronal cell bodies in both mice and human. Somatic microglia-neuron junctions are present on the vast majority of cortical neurons, independently of their neurochemical identity, and possess a unique ultrastructure that is ideal for purinergic communication. In response to elevated neuronal activity and brain injury, the ultrastructure of somatic junctions is altered and signalling via microglial purinergic P2Y12 receptors is required for microglia-mediated responses. Blockade of P2Y12 receptors leads to elevated neuronal calcium-load and increased infarct volume following experimental stroke.
Conclusion: These newly identified somatic microglia-neuron junctions are positioned ideally for microglia to monitor and shape neuronal activity. The presence of these junctions on most neurons suggests that these structures may serve as a previously unidentified quality control system in the brain. Better understanding of microglia-neuron bidirectional communication is necessary for the development of efficient therapeutic approaches to neurodegenerative diseases.
Doctoral School: János Szentágothai Doctoral School of Neurosciences
Program: Neuromorphology and Cell Biology
Supervisor: Ádám Dénes, Csaba Cserép
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