The role of astrocytes in brain circuitry function, such as swift glutamate release, has been questioned due to inconsistent data and lack of direct evidence. This mechanism, similar to neurons, controls plasticity, excitability, and coordinated activity of synaptic-type networks but also contributes to neuropsychiatric conditions.
A cross-species evaluation was performed by referencing three hippocampal cell databases. fluorescence in-situ hybridization analysis was performed to analyze hippocampal slices from adult murine cells co-immunostained with astrocytic markers such as GS and S100β. The researchers applied clozapine N-oxide through brief puffs locally followed by L-glutamate application as a control. To determine whether astrocyte release occurred through exocytosis, the team sought to impede glutamate filling in vesicles.
Related StoriesThey also discovered a matching astrocyte subgroup that reliably reacted to astrocyte-specific stimulations with sub-second release of glutamate at geographically specific areas of greatest need, which was inhibited by astrocyte-targeted VGLUT1 ablation. Glutamate release responses always took place at specific hotspots of an astrocyte, providing direct functional evidence for the existence of a specialized population of glutamatergic astrocytes predicted by transcriptomic studies. The team found a robust correlation between the physiological and molecular identification of glutamatergic astrocytes.
Astrocyte VGLUT2-dependent signaling regulated nigrostriatal dopaminergic pathway function in vivo, representing a potential therapeutic target for Parkinson's disease.