title: Single-nanotube tracking reveals the nanoscale organization of the extracellular space in the live brain.
abstract: The brain is a dynamic structure with the extracellular space (ECS) taking up almost a quarter of its volume. Signalling molecules, neurotransmitters and nutrients transit via the ECS, which constitutes a key microenvironment for cellular communication and the clearance of toxic metabolites. The spatial organization of the ECS varies during sleep, development and aging and is probably altered in neuropsychiatric and degenerative diseases, as inferred from electron microscopy and macroscopic biophysical investigations. Here we show an approach to directly observe the local ECS structures and rheology in brain tissue using super-resolution imaging. We inject single-walled carbon nanotubes into rat cerebroventricles and follow the near-infrared emission of individual nanotubes as they diffuse inside the ECS for tens of minutes in acute slices. Because of the interplay between the nanotube geometry and the ECS local environment, we can extract information about the dimensions and local viscosity of the ECS. We find a striking diversity of ECS dimensions down to 40 nm, and as well as of local viscosity values. Moreover, by chemically altering the extracellular matrix of the brains of live animals before nanotube injection, we reveal that the rheological properties of the ECS are affected, but these alterations are local and inhomogeneous at the nanoscale.
authors.affiliation: Laboratoire Photonique Numérique et Nanosciences, Univ. Bordeaux, UMR 5298, F-33400 Talence, France.|Institut d'Optique &CNRS, LP2N UMR 5298, F-33400 Talence, France.
authors.forename: Antoine G
authors.initials: AG
authors.lastname: Godin
authors.affiliation: Univ. Bordeaux, Interdisciplinary Institute for Neuroscience, UMR 5297, F-33000 Bordeaux, France.|CNRS, IINS UMR 5297, F-33000 Bordeaux, France.
authors.forename: Juan A
authors.identifier: 0000-0003-1901-1378
authors.initials: JA
authors.lastname: Varela
authors.affiliation: Laboratoire Photonique Numérique et Nanosciences, Univ. Bordeaux, UMR 5298, F-33400 Talence, France.|Institut d'Optique &CNRS, LP2N UMR 5298, F-33400 Talence, France.
authors.forename: Zhenghong
authors.initials: Z
authors.lastname: Gao
authors.affiliation: Laboratoire Photonique Numérique et Nanosciences, Univ. Bordeaux, UMR 5298, F-33400 Talence, France.|Institut d'Optique &CNRS, LP2N UMR 5298, F-33400 Talence, France.
authors.forename: Noémie
authors.initials: N
authors.lastname: Danné
authors.affiliation: Univ. Bordeaux, Interdisciplinary Institute for Neuroscience, UMR 5297, F-33000 Bordeaux, France.|CNRS, IINS UMR 5297, F-33000 Bordeaux, France.
authors.forename: Julien P
authors.initials: JP
authors.lastname: Dupuis
authors.affiliation: Laboratoire Photonique Numérique et Nanosciences, Univ. Bordeaux, UMR 5298, F-33400 Talence, France.|Institut d'Optique &CNRS, LP2N UMR 5298, F-33400 Talence, France.
authors.forename: Brahim
authors.initials: B
authors.lastname: Lounis
authors.affiliation: Univ. Bordeaux, Interdisciplinary Institute for Neuroscience, UMR 5297, F-33000 Bordeaux, France.|CNRS, IINS UMR 5297, F-33000 Bordeaux, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Groc
authors.affiliation: Laboratoire Photonique Numérique et Nanosciences, Univ. Bordeaux, UMR 5298, F-33400 Talence, France.|Institut d'Optique &CNRS, LP2N UMR 5298, F-33400 Talence, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Cognet
mesh_terms: D000818:Animals; D060833:Cellular Microenvironment; D002552:Cerebral Ventricles / Q000000981:diagnostic imaging*; D005110:Extracellular Space / Q000000981:diagnostic imaging*; D037742:Nanotubes, Carbon / Q000737:chemistry*; D061848:Optical Imaging / Q000379:methods*; D011092:Polyethylene Glycols / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D037742:Nanotubes, Carbon; D011092:Polyethylene Glycols