Model of extracellular diffusion in layered structure of hippocampus

1. Introduction The extracellular space (ECS) surrounding neurons and glia facilitates diffusion of nutrients, neurotransmitters, metabolites, and pharmaceuticals in the brain. Measurements of extracellular diffusion with methods such as real-time iontophoresis (RTI) [1] reveal that the ECS typically comprises about 20% of tissue volume (i.e. the ECS volume fraction α = V ECS /V tissue is typically ≈ 0.2) and diffusion permeability D ECS is typically about 40% of that in an obstacle-free medium (θ = D ECS /D free is typically ≈ 0.4) [2]. In the CA1 region of the hippocampus, a thin layer (≈ 50 µm) of tightly packed pyramidal cell bodies (stratum pyramidale or SP) separates the stratum oriens (SO) and stratum radiatum (SR) layers (see Fig. 1). This thin SP layer impedes extracellular diffusion [3]. We developed a model of extracellular diffusion in layered structures in order to estimate α and θ in the SP layer of rat hippocampus from RTI data reported in [3]. In these experiments, tetramethylammonium (TMA +) ions were released into CA1 by iontophoresis from a source electrode and detected with an ion-selective probe electrode about 100 µm away. The usual assumption of homogeneous diffusion environment is not valid for the SP layer because it is thinner than the electrode spacing.