Calcium controls the wanderings of receptors in neuronal membranes

Paris, June 26, 2002

Memorization and learning processes involve a modification in the efficacy of information transmission between neurons, or "synaptic plasticity." Understanding the mechanisms underlying this plasticity is one of the major areas of current research into how the brain functions. The concentration of neurotransmitter receptors in synapses is one of the key parameters in synaptic efficacy. By combining physics and biology techniques, Aren J. Borgdorff et Daniel Choquet, CNRS researchers , have successfully visualized the movement of certain receptors in the neuronal membranes. These results, published in the June 6, 2002 issue of Nature, emphasize the decisive role played by calcium in mobilizing and grouping together receptors in synapses and thus probably in the processes of synaptic plasticity.

Glutamate is the main neurotransmitter in the excitatory synapses of the nervous system. Aren J. Borgdorff and Daniel Choquet have opened up a new avenue of research by observing the movement of a family of glutamate receptors on the neuronal surface in real time. These receptors are in perpetual motion and their movements are strongly controlled by neuronal activity. But how can these receptors enter and exit from the synapses?

Work published in 2001 and 2002 by the "Laboratoire de physiologie cellulaire de la synapse" (Cellular Physiology of the Synapse Laboratory) in Bordeaux has established that the movement of receptors on the neuronal surface is reduced considerably by intracellular stabilization proteins, which are also responsible for enriching the receptors in the synapses .

Today, Daniel Choquet and his team are developing a set of new tools for real-time viewing of the movement of receptors on the surfaces of cultured neurons forming synaptic clusters. In particular, they are using tiny 500 nm latex beads coated with antibodies that bind to certain receptors, the beads being faithful witnesses to the movement of the receptors. These tiny beads are handled using laser tweezers in order to position them with great precision on the surfaces of the cells. The researchers have also produced an optical setup that is probably unique in the world, with two white light sources and two laser beams of different colors. They have succeeded simultaneously in manipulating and viewing the particles, in viewing fluorescent proteins, and in locally stimulating the receptors.

The work by Aren Bordgorff and Daniel Choquet shows that glutamate receptors are continuously moving on the neuronal surface, with alternating periods of rapid diffusive movement and stationary periods. The stationary periods generally occur close to the synapses, which would suggest that the receptors enter into and exit from the synaptic sites frequently by lateral diffusion in the plane of the membrane.

The high point of this research has been the observation of local variations in intracellular calcium that are capable, firstly, of very rapidly immobilizing the diffusing receptors, and, secondly, of leading, in a few minutes, to a major local buildup of these receptors. This result demonstrates that calcium, a second messenger playing a decisive role in the processes of synaptic plasticity, is capable of modifying the local concentration of receptors by modulating their lateral diffusion in the plane of the membrane.

The local concentration of receptors in the membrane is controlled by molecules capable of modifying their diffusion or their stabilization on the neuronal surface.

Reference: Borgdorff, A., and Choquet, D. (2002). Regulation of AMPA receptor lateral movements. Nature, June 6, 2002.

CNRS researcher contact
Daniel Choquet
Tel: +33 5 57 57 40 90 - Fax: +33 5 57 57 40 82
e-mail: daniel.choquet@u-bordeaux2.fr

CNRS Life Sciences Department contact
Marie-Pascale Corneloup-Brossollet
Tel: +33 1 44 96 46 48 - Fax: +33 1 44 96 49 19
e-mail: marie.corneloup@cnrs-dir.fr

CNRS press contact
Stéphanie BIA
Tel: +33 1 44 96 43 09
e-mail: stephanie.bia@cnrs-dir.fr