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Valentin Nägerl's team dans Nature Neuroscience

Spine necks: no small matter

Le 24 mars 2014

Spine neck plasticity regulates compartmentalization of synapses
Nature Neuroscience. doi:10.1038/nn.3682 Authors: Jan Tønnesen, Gergely Katona, Balázs Rózsa & U Valentin Nägerl […] Sun, Mar 23, 2014
1Interdisciplinary Institute for Neuroscience (IINS), Université de Bordeaux, France 
2UMR 5297, Centre National de la Recherche Scientifique (CNRS), Bordeaux, France
3Two-photon Imaging Center, Institute of Experimental Medicine of the Hungarian Academy of Sciences, Budapest, Hungary *Corresponding author

 


The team of Valentin Nägerl at the University of Bordeaux has discovered a novel structural mechanism by which neurons can rapidly tune their synapses in response to stimulation.
The study will appear online in the journal Nature Neuroscience on March 20, 2014 (DOI 10.1038/nn.3682).

The ability to adapt its functional architecture is a fundamental property of the central nervous system, which is thought to be important for behaviour, nervous system plasticity and human brain diseases. Neurons are functionally connected with each other by thousands of synapses, which typically are formed on dendritic spines. Spines are tiny protrusions in the postsynaptic membrane, which house the complex molecular machinery of synapses. They have a conspicuous, mushroom-like morphology, featuring a bulbous head, which is linked to the parent dendrite via a long and thin stalk, called the spine neck, which is thought to be critical for synapse function. Because spine necks are superthin (around 150 nm, which is about 1/1000 the width of a human hair), it has been impossible to image them using regular light microscopy.

Using superresolution STED microscopy, Dr. Jan Tonnesen, a postdoctoral researcher in the Nägerl team, was able to visualize spine necks in living brain tissue and track their dynamics in real time. In combination with electrophysiological and biophysical approaches, he discovered that spine necks rapidly become wider and shorter in response to strong synapse activation, and that this structural remodelling substantially impacts signal transduction at synapses.


Figure: STED image of dendritic spines (left), scale bar 500 nm; concurrent FRAP experiment to measure diffusional coupling between spines and dendrite (right).

Taken together, the study provides direct evidence for the long-standing hypothesis that spine necks, far from being mere anatomical fixtures, represent dynamic nanoscale valves that dynamically control the flow of electrochemical signals in and out of synapses.  Using their powerful microscope the researchers intend to zoom in on other key nanoscale neural structures, such as axons and glial processes, hoping to unveil their secrets..

 ABSTRACT
Dendritic spines have been proposed to transform synaptic signals through chemical and electrical compartmentalization. However, the quantitative contribution of spine morphology to synapse compartmentalization and its dynamic regulation are still poorly understood.

We used time-lapse superresolution STED imaging in combination with FRAP measurements, 2-photon glutamate uncaging, electrophysiology and simulations to investigate the dynamic link between nanoscale anatomy and compartmentalization in live spines of CA1 neurons in mouse brain slices. 

We report a diversity of spine morphologies that argues against common categorization schemes, and establish a close link between compartmentalization and spine morphology, where spine neck width is the most critical morphological parameter. We demonstrate that spine necks are plastic structures that become wider and shorter after LTP. These morphological changes are predicted to lead to a substantial drop in spine head EPSP, while leaving overall biochemical compartmentalization preserved.

 

Valentin Nägerl (valentin.nagerl @ u-bordeaux.fr)
Dernière mise à jour le 24.03.2014

First author



Jan Tonnesen
Post-doctoral researcher
Research Team: Synaptic Plasticity and Superresolution Microscopy - U. Valentin Nägerl 
Institut interdisciplinaire de Neurosciences
CNRS UMR 5297
Université Bordeaux
jan.tonnesen@u-bordeaux.fr