The role of the brain extracellular space in diffusion and cell signalling

Abstract

The extracellular space (ECS) is a highly complex space consisting of narrow interconnected channels and reservoirs. The ECS substructures are usually few nanometers wide and consequently, they are very difficult to visualize. In addition, the brain ECS is a very dynamic structure, that changes at different temporal scales. These structural changes can be physiological or they can have a pathological cause. In fact, astrocytic swelling at the expense of the ECS volume is one of the hallmarks of epilepsy. Particularly, we are interested in how ECS volume changes affect GABAergic inhibition, the main source of inhibition in the brain and one of the most studied processes in the onset of epileptogenesis.On the other hand, most intercellular signalling in the brain occurs by diffusion of particles through the ECS channels. Understanding how diffusion is regulated by the fine geometry of the brain neuropil is becoming the focus of interest for researchers. However, progress in this field is limited by the difficulty to access local ECS diffusion with experimental techniques. Recently developed techniques, such as super-resolution shadow imaging (SUSHI), are opening the doors to understand diffusion of molecules through the brain sub-micron ECS structures. In this study, we aim to investigate how the nano-scale ECS geometry of the live brain tissue shapes the diffusion of transmitters and its impact on cellular communication. To attain this goal, we have developed a novel computational model, based on SUSHI images.