Microglial Displacement of GABAergic Synapses Is a Protective Event during Complex Febrile Seizures.

Abstract:

:Complex febrile seizures (FSs) lead to a high risk of intractable temporal lobe epilepsy during adulthood, yet the pathological process of complex FSs is largely unknown. Here, we demonstrate that activated microglia extensively associated with glutamatergic neuronal soma displace surrounding GABAergic presynapses in complex FSs. Patch-clamp electrophysiology establishes that the microglial displacement of GABAergic presynapses abrogates a complex-FS-induced increase in GABAergic neurotransmission and neuronal excitability, whereas GABA exerts an excitatory action in this immature stage. Pharmacological inhibition of microglial displacement of GABAergic presynapses or selective ablation of microglia in CD11bDTR mice promotes the generation of complex FSs. Blocking or deleting the P2Y12 receptor (P2Y12R) reduces microglial displacement of GABAergic presynapses and shortens the latency of complex FSs. Together, microglial displacement of GABAergic presynapses, regulated by P2Y12R, reduces neuronal excitability to mitigate the generation of complex FSs. Microglial displacement is a protective event during the pathological process of complex FSs.

journal_name

Cell Rep

journal_title

Cell reports

authors

Wan Y,Feng B,You Y,Yu J,Xu C,Dai H,Trapp BD,Shi P,Chen Z,Hu W

doi

10.1016/j.celrep.2020.108346

subject

Has Abstract

pub_date

2020-11-03 00:00:00

pages

108346

issue

5

issn

2211-1247

pii

S2211-1247(20)31335-8

journal_volume

33

pub_type

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