The receptors of neurotransmitters move very rapidly. This mobility plays an essential, and hitherto unsuspected, role in the passage of nerve impulses from one neuron to another, thus controlling the reliability of data transfer. This has recently been demonstrated by scientists in the "Physiologie cellulaire de la synapse" Laboratory (CNRS/Université Bordeaux 2) coordinated by Daniel Choquet, senior researcher at CNRS.
By enabling a clearer understanding of the mechanisms involved in neuronal transmissions, this work opens the way to new therapeutic targets for the neurological and psychiatric disorders that depend on poor neuronal communication (Parkinson's disease, Alzheimer's disease, OCD, etc.). Fruit of a collaboration with physicists in the Centre de physique moléculaire optique et hertzienne (CPMOH, CNRS/Université Bordeaux 1) and German and American research teams(1), these findings were published on April 11, 2008 in Science.
The processing of information by the brain is mainly based on the coding of data by variations in the frequency of neuronal activity. "Good" communication thus implies the reliable transmission of this "code" by the connections between neurons, or synapses. Under normal circumstances, this junction comprises a pre-synaptic element from which the information arises, and a post-synaptic element which receives it.
It is at this point that neuronal communication occurs. Once the pre-synaptic neuron has been stimulated by an electrical signal with a precise frequency, it releases chemical messengers into the synapse: neurotransmitters. And the response is rapid! These neurotransmitters bind to specific receptors, thus provoking a change to the electrical activity of the post-synaptic neuron and hence the birth of a new signal.
The mobility of receptors controls the reliability of neuronal transmission. Working at the interface between physics and biology, the teams in Bordeaux led by Choquet, CNRS senior researcher in the "Physiologie cellulaire de la synapse"(2) laboratory, working in close collaboration with the group led by
Brahim Lounis at the Centre de physique moléculaire optique et hertzienne(2) have been studying synaptic transmission and, more particularly, the role of certain receptors of glutamate, a neurotransmitter present in 80% of neurons in the brain.
Focusing on the dynamics of these receptors, the researchers have revealed that a minor modification to their mobility has a major impact on high frequency synaptic transmission, i.e. at frequencies between 50 and 100 Hz (those which intervene during memorization, learning or sensory stimulation processes). More specifically, they have established that this mobility enables the replacement in a few milliseconds of desensitized receptors by "naïve" receptors in the synapse. This phenomenon reduces synaptic depression(3) and allows the neurons to transmit the information at a higher frequency. By contrast, if the receptors are immobilized, this depression is notably enhanced, preventing transmission of the nerve impulse in the synapses above around ten Hertz.
More profoundly, the scientists have demonstrated that prolonged series of high frequency stimulations, which induce an increase in calcium levels in the synapses, cause the immobilization of receptors. They have also proved that these series of stimulations diminish the ability of neurons to transmit an activity at high frequency. Receptor mobility is thus correlated with the frequency of synaptic transmission and consequently, the reliability of this transmission.
A real advance for research
When the brain is functioning under normal conditions, we can suppose that the immobilization of receptors following a series of high frequency stimulations constitutes a safety mechanism. It will prevent subsequent series from overexciting the post-synaptic neuron. A reliable transmission of information between two neurons is obviously crucial to satisfactory functioning of the brain.
These results, of prime importance, suggest that some dysfunctions of neuronal transmission are due to a defect in receptor stabilization. However, high frequency electrical stimulation of certain regions of the brain is used to treat Parkinson's disease or obsessive-compulsive disorders (OCD). Its mechanism of action, still poorly understood, may therefore involve receptor mobility. This work has thus made it possible to identify new therapeutic targets and could augur well for potential drugs to treat neurological and psychiatric disorders which often result from poor communication between neurons.
Journal reference: Surface Mobility of Post-synaptic AMPARs Tunes Synaptic Transmission. Martin Heine, Laurent Groc, Renato Frischknecht, Jean-Claude Béïque, Brahim Lounis, Gavin Rumbaugh, Richard L. Huganir, Laurent Cognet and Daniel Choquet. Science. 11 April 2008.
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