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Super dimensional scenery
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Super dimensional scenery
Neurological overexcitement is a common pathological feature of many neurological diseases, such as when external stressors such as infections, trauma, or toxins stimulate the brain, neuronal networks typically exhibit overexcitement accompanied by synaptic reorganization. Many neurological disorders have similar phenomena, such as Alzheimer's disease (AD), autism spectrum disorder, schizophrenia, tuberous sclerosis, especially in epilepsy. There are many explanations for the mechanism of neuronal overexcitement, among which the imbalance between excitatory (mainly glutamatergic) and inhibitory (mainly gamma aminobutyric) synaptic transmission (E/I imbalance) is considered a key one; However, the mechanism of neuronal glial interaction is still unclear.
On May 27, 2025, Yan Chao and Liu Xiangyu from Nanjing University, Cong Qifei from Suzhou University, and Li Xinjian from Zhejiang University jointly published a research paper titled "GABA dependent microglial elimination of inhibitory synapses underlying neural hyperexcitability in epilepsy" online in Nature Neuroscience (IF=21.3). They successfully achieved stable in vivo observation of calcium signals in epileptic mouse microglia using a high-dimensional miniaturized two-photon microscopy imaging system (FHIRM series), revealing the key role of microglia mediated selective elimination of inhibitory synapses in driving neuronal overexcitation.

Screenshot of the online publication of the paper
After establishing a mouse model of temporal lobe epilepsy (TLE) in CX3CR1-GCaMP6s transgenic mice, researchers used miniaturized two-photon technology for temporal lobe two-photon calcium imaging and found that after induction with kainic acid (KA), the calcium signal of microglia in the temporal lobe cortex significantly increased. After administering a GABAB receptor antagonist CGP52432 via intraperitoneal injection, this activation phenomenon can be greatly inhibited, indicating that GAGB signaling plays a role in the response of microglia. This has laid a solid foundation for the subsequent confirmation that the activation and clearance of inhibitory synapses by microglia lead to neuronal hyperexcitability in epilepsy.

This study not only deepens the understanding of the neuroimmune mechanisms of epilepsy, but also highlights the value of precise imaging tools in neuroscience research. We are honored to provide imaging technology support for this important research.
[Reference]
Chen ZP, Zhao X, Wang S, et al. GABA-dependent microglial elimination of inhibitory synapses underlies neuronal hyperexcitability in epilepsy. Nat Neurosci. Published online May 27, 2025. doi:10.1038/s41593-025-01979-2