Cell-specific IL-1R1 regulates the regional heterogeneity of microglial displacement of GABAergic synapses and motor learning ability

© 2024. The Author(s)..

Microglia regulate synaptic function in various ways, including the microglial displacement of the surrounding GABAergic synapses, which provides important neuroprotection from certain diseases. However, the physiological role and underlying mechanisms of microglial synaptic displacement remain unclear. In this study, we observed that microglia exhibited heterogeneity during the displacement of GABAergic synapses surrounding neuronal soma in different cortical regions under physiological conditions. Through three-dimensional reconstruction, in vitro co-culture, two-photon calcium imaging, and local field potentials recording, we found that IL-1β negatively modulated microglial synaptic displacement to coordinate regional heterogeneity in the motor cortex, which impacted the homeostasis of the neural network and improved motor learning ability. We used the Cre-Loxp system and found that IL-1R1 on glutamatergic neurons, rather than that on microglia or GABAergic neurons, mediated the negative effect of IL-1β on synaptic displacement. This study demonstrates that IL-1β is critical for the regional heterogeneity of synaptic displacement by coordinating different actions of neurons and microglia via IL-1R1, which impacts both neural network homeostasis and motor learning ability. It provides a theoretical basis for elucidating the physiological role and mechanism of microglial displacement of GABAergic synapses.

Medienart:

E-Artikel

Erscheinungsjahr:

2024

Erschienen:

2024

Enthalten in:

Zur Gesamtaufnahme - volume:81

Enthalten in:

Cellular and molecular life sciences : CMLS - 81(2024), 1 vom: 04. März, Seite 116

Sprache:

Englisch

Beteiligte Personen:

You, Yi [VerfasserIn]
An, Da-Dao [VerfasserIn]
Wan, Yu-Shan [VerfasserIn]
Zheng, Bai-Xiu [VerfasserIn]
Dai, Hai-Bin [VerfasserIn]
Zhang, She-Hong [VerfasserIn]
Zhang, Xiang-Nan [VerfasserIn]
Wang, Rong-Rong [VerfasserIn]
Shi, Peng [VerfasserIn]
Jin, Mingjuan [VerfasserIn]
Wang, Yi [VerfasserIn]
Jiang, Lei [VerfasserIn]
Chen, Zhong [VerfasserIn]
Hu, Wei-Wei [VerfasserIn]

Links:

Volltext

Themen:

Calcium
Displacement
Homeostasis
Interleukin-1beta
Journal Article
Microglia
Motor learning
SY7Q814VUP
Synapse

Anmerkungen:

Date Completed 06.03.2024

Date Revised 07.03.2024

published: Electronic

Citation Status MEDLINE

doi:

10.1007/s00018-023-05111-0

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM369286715