Nanoscale and functional heterogeneity of the hippocampal extracellular space
Diego Grassi,
Agata Idziak,
Antony Lee,
Ivo Calaresu,
Jean-Baptiste Sibarita,
Laurent Cognet,
U. Valentin Nägerl,
Laurent Groc
Affiliations
Diego Grassi
University of Bordeaux, CNRS, Interdisciplinary Institute for Neuroscience, IINS, UMR 5297, 33000 Bordeaux, France
Agata Idziak
University of Bordeaux, CNRS, Interdisciplinary Institute for Neuroscience, IINS, UMR 5297, 33000 Bordeaux, France
Antony Lee
University of Bordeaux, Laboratoire Photonique Numérique et Nanosciences (LP2N), UMR 5298, 33400 Talence, France; Institut d’Optique & CNRS, LP2N UMR 5298, 33400 Talence, France
Ivo Calaresu
University of Bordeaux, CNRS, Interdisciplinary Institute for Neuroscience, IINS, UMR 5297, 33000 Bordeaux, France
Jean-Baptiste Sibarita
University of Bordeaux, CNRS, Interdisciplinary Institute for Neuroscience, IINS, UMR 5297, 33000 Bordeaux, France
Laurent Cognet
University of Bordeaux, Laboratoire Photonique Numérique et Nanosciences (LP2N), UMR 5298, 33400 Talence, France; Institut d’Optique & CNRS, LP2N UMR 5298, 33400 Talence, France
U. Valentin Nägerl
University of Bordeaux, CNRS, Interdisciplinary Institute for Neuroscience, IINS, UMR 5297, 33000 Bordeaux, France
Laurent Groc
University of Bordeaux, CNRS, Interdisciplinary Institute for Neuroscience, IINS, UMR 5297, 33000 Bordeaux, France; Corresponding author
Summary: The extracellular space (ECS) and its constituents play a crucial role in brain development, plasticity, circadian rhythm, and behavior, as well as brain diseases. Yet, since this compartment has an intricate geometry and nanoscale dimensions, its detailed exploration in live tissue has remained an unmet challenge. Here, we used a combination of single-nanoparticle tracking and super-resolution microscopy approaches to map the nanoscale dimensions of the ECS across the rodent hippocampus. We report that these dimensions are heterogeneous between hippocampal areas. Notably, stratum radiatum CA1 and CA3 ECS differ in several characteristics, a difference that gets abolished after digestion of the extracellular matrix. The dynamics of extracellular immunoglobulins vary within these areas, consistent with their distinct ECS characteristics. Altogether, we demonstrate that ECS nanoscale anatomy and diffusion properties are widely heterogeneous across hippocampal areas, impacting the dynamics and distribution of extracellular molecules.
