Nanoscale and functional heterogeneity of the hippocampal extracellular space
Cell Reports. 2023-05-01; 42(5): 112478
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Grassi D(1), Idziak A(1), Lee A(2), Calaresu I(1), Sibarita JB(1), Cognet L(2), Nägerl UV(1), Groc L(3).
(1)University of Bordeaux, CNRS, Interdisciplinary Institute for Neuroscience,
IINS, UMR 5297, 33000 Bordeaux, France.
(2)University of Bordeaux, Laboratoire Photonique Numérique et Nanosciences
(LP2N), UMR 5298, 33400 Talence, France; Institut d’Optique & CNRS, LP2N UMR
5298, 33400 Talence, France.
(3)University of Bordeaux, CNRS, Interdisciplinary Institute for Neuroscience,
IINS, UMR 5297, 33000 Bordeaux, France. Electronic address:
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.
Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.
Conflict of interest statement: Declaration of interests The authors declare no