March 9, 2018 Friday Lunch Seminar
12:15 〜 13:00
CiNet 1F Conference Room
“Brain temperature stimulates microglia to modulate synaptic connections”
Graduate School of Pharmaceutical Sciences
Faculty of Pharmaceutical Sciences,
The University of Tokyo
Host PI : Yuji Ikegaya
Hyperthermia (typically greater than 38°C)-induced febrile seizures are the most common type of seizures in early childhood. Prolonged febrile seizures could induce the development of epilepsy by disrupting the excitatory versus inhibitory balance (E/I balance) of synapses; however the cellular and molecular link between hyperthermia and E/I imbalance is missing. Here we report that microglia disrupt the synapse E/I balance in dentate gyrus networks with the phagocytic capacity. Microglia detected the increase in brain temperature during experimental febrile seizures by the Ca2+-influx through activation of transient receptor potential vanilloid 4 (TRPV4), which is a thermosensor highly activated by heat (>34°C). The TRPV4 activation stimulated microglia to preferentially engulf inhibitory synapses in neuronal activity- and complement-dependent mechanisms, rendering the dentate gyrus networks hyperexcitable. Finally, a blood-brain barrier-permeable TRPV4 antagonist decreased the febrile seizure-induced seizure severity. Thus, our study provides a novel mechanism by which the brain hyperthermia impairs the synapse E/I balance via activation of microglia.
About CiNet’s Friday Lunch Seminars:
The Friday Lunch Seminar is CiNet’s main regular meeting series, held every week at 12:15 in the beautiful main lecture theatre on the ground floor at CiNet. The talks are typically 40mins long and orientated towards an inter-disciplinary audience. They are informal, social, and most people bring their own lunch to eat during the talk. They are open to anyone who is feeling curious and wants to come, regardless of where you work.