Stochastic tissue environment expands spatial limits of synaptic and astrocytic glutamate actions

The preprint operates within the dominant paradigm of neuroscience, which emphasizes the precise point-to-point transmission of glutamate at synapses. This paradigm is based on the understanding that high-affinity astrocytic transporters restrict glutamate spread, ensuring the specificity of synaptic signaling.

This preprint presents a refined computational model of glutamate diffusion in the synaptic neuropil. It challenges the simplified assumption of uniform transporter distribution around synapses, introducing a stochastically generated tissue environment that more accurately reflects the complex arrangement of cellular structures and transporter-expressing astrocytic processes. This refinement leads to the prediction of a wider glutamate spread than previously estimated, suggesting potential spillover effects on neighboring synapses. However, the preprint doesn't fundamentally challenge the existing paradigm. Instead, it operates within the framework of normal science by elaborating and refining the existing model to better explain experimental observations of extrasynaptic glutamate actions. The study's conclusions highlight the need for further experimental investigation to determine the physiological implications of its findings, particularly regarding the less-understood phenomenon of astrocytic glutamate release. The authors suggest potential implications for volume transmission but acknowledge that the physiological role of this remains largely unexplored.