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RTD info logoMagazine on European Research Special Issue - April 2005   
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MEMORY MECHANISMS
Title  Inside the memory machine

Despite progress made in describing the biochemical mechanisms of memory, when it comes to neuron networks how we remember remains an enigma. This was just one of the conclusions reached at the two Euresco conferences held in 2002 and 2004 on the subject of memory and learning.

The drosophila is again the focus of scientific attention, this time yielding the secrets of its short-term memory. © INSERM/A.Alberga
The drosophila is again the focus of scientific attention, this time yielding the secrets of its short-term memory. © INSERM/A.Alberga
The drosophila is again the focus of scientific attention, this time yielding the secrets of its short-term memory.
© INSERM/A.Alberga
In contrast to the rather formal gatherings often organised by international learned societies, the Euresco conferences, organised by the European Science Foundation with European Union support, favour in-depth discussion and the participation of young researchers. The second Euresco conference on the subject of memory and learning, held in Obernai (FR) in May 2004, once again showed how these meetings could act as a crucible for the European Research Area. As chairman of the proceedings, Randolf Menzel, professor of neurobiology at the Free University of Berlin, explained, “a number of colleagues told me that they recruited their future students at this conference, and I know several examples of European projects that originated at one of these Euresco meetings”.    

The coincidence detector
Three decades after the first description of long-term potentiation or LTP – the memory mechanism that is thought to boost the efficiency of the most active synapses – what are the principal scientific developments in this fast-expanding field? Menzel identified two: the biochemical and cellular description of LTP and the study of its significance in the context of neuron networks. 

On the first of these two fronts, knowledge of the various glutamate (principal neurotransmitter within the central nervous system) receptors has increased greatly. One of these receptors, known as NMDA – after one of the molecules (N-Methyl D-Aspartate) that activates it – has the surprising property of only allowing calcium ions to pass through on two conditions: if the neuronal membrane is depolarised and if glutamate is present. As a result, in the 1980s, this receptor came to be known as the ‘coincidence detector’. If the neuron receives a new excitatory signal (glutamate) when it is already excited (cellular depolarisation), the NMDA receptor allows calcium to enter which, in turn, activates a series of genes that are, ultimately, responsible for strengthening the synapse efficiency. “But note,” warns Menzel, “we now know other molecules, intracellular enzymes or receptors, whose biochemical properties also correspond to this role of coincidence detector.” 

Return of the drosophila
So how does their action relate to that of the NMDA receptor? In answering this question, we leave the realms of cellular neurobiology to enter that of memory research and the puzzle of neuron networks. “In this field, progress over the past decade has been slower,” continues Menzel, who admits there is a “huge gap” in our knowledge of the in vitro functioning of the LTP and the memory mechanisms at work in our brain.

How can we fill this gap? The discussions at the Euresco conference in Obernai highlighted two essential approaches. The learning behavioural models need to be further refined (the Edvard Moser(1) working group was welcomed as making a major contribution to this), and biotechnological tools to activate or deactivate as desired the expression of the gene coding for glutamate receptors need to be developed.

The Euresco conference also presented the occasion to discuss a recent exciting discovery: the creation of short-term memory in the drosophila. The data presented in Obernai showed that all that is involved in creating an olfactory memory in this insect is a neuron population that sends axons to the cerebral peduncles, just a small region of the brain. “Does this discovery call into question the commonly accepted idea of memory that is widely distributed in the brain? And what is the link between this short-term memory and the creation of a long-term memory?” asks Menzel.

In any case, one thing seems clear: it would be a mistake to view this discovery as a zoological curiosity of the drosophila because, as Professor Menzel stresses, “from the aplysia or the drosophila, to the bee and on to the Caenorhabditis elegans, most of these major discoveries in the neurosciences were first made on invertebrates before being extended to mammals.” 

(1) See The nuts and bolts of remembering.

    
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