Targeting neurotransmitter receptors with nanoparticles in vivo allows single-molecule tracking in acute brain slices
Nat Commun. 2016-03-14; 7(1):
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Varela JA(1)(2), Dupuis JP(1)(2), Etchepare L(1)(2), Espana A(1)(2), Cognet L(3)(4), Groc L(1)(2).
(1)University of Bordeaux, Interdisciplinary Institute for Neuroscience, UMR5297, Bordeaux F-33000, France.
(2)CNRS, IINS UMR 5297, Bordeaux F-33000, France.
(3)University of Bordeaux, LP2 NUMR 5298, Talence F-33405, France.
(4)Institut d’Optique &CNRS, LP2NUMR 5298, Talence F-33405, France.
Single-molecule imaging has changed the way we understand many biological
mechanisms, particularly in neurobiology, by shedding light on intricate
molecular events down to the nanoscale. However, current single-molecule studies
in neuroscience have been limited to cultured neurons or organotypic slices,
leaving as an open question the existence of fast receptor diffusion in intact
brain tissue. Here, for the first time, we targeted dopamine receptors in vivo
with functionalized quantum dots and were able to perform single-molecule
tracking in acute rat brain slices. We propose a novel delocalized and
non-inflammatory way of delivering nanoparticles (NPs) in vivo to the brain,
which allowed us to label and track genetically engineered surface dopamine
receptors in neocortical neurons, revealing inherent behaviour and receptor
activity regulations. We thus propose a NP-based platform for single-molecule
studies in the living brain, opening new avenues of research in physiological and
pathological animal models.