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Still searching for the engram: Should we?

Fourth Sym­posium on Open ques­tions in Neuroscience

Center for Neurophysics, Physiology et Pathology

December, 10, 2014

In the Traité de l’Homme, Descartes described the brain as a com­plex mesh of tiny tubes along which dif­fer­ent flow­ing pat­terns of ‘ani­mal spir­its’ could be phys­i­cal­ly real­ized, each cor­re­spond­ing to spe­cif­ic sen­so­ry infor­ma­tion or motor com­mands. As the spir­its flowed through, they caused per­sis­tent struc­tur­al mod­i­fi­ca­tions of the tubes, that would in turn change the pat­tern in which the spir­its would lat­er flow, and — Descartes con­clud­ed — “c’est en quoi con­siste la mémoire” [this is what mem­o­ry con­sists of]. Clear­ly wrong in the phys­i­o­log­i­cal details, Descartes’ account nev­er­the­less ush­ered in the basic con­cepts that inform cur­rent research about mem­o­ry mech­a­nisms. As Lash­ley famous­ly wrote: “Sub­sti­tute nerve impulse for ani­mal spir­its, synapse for pore [tube] and the result is the doc­trine of learn­ing as change in resis­tance of synaps­es”. The mod­ern notion, epit­o­mized in Hebb’s dual-trace the­o­ry, is that mem­o­ries are stored by activ­i­ty-dri­ven changes in the pat­tern and strengths of the con­nec­tions between a sub-set of neu­rons in the brain (the engram), and their per­sis­tence over time results from the con­sol­i­da­tion of those struc­tur­al changes.

Recent exper­i­men­tal results have pro­vid­ed mixed sup­port for this synap­tic trace the­o­ry of mem­o­ry. In our opin­ion, they raise in fact more ques­tions than pro­vide answers. Chron­ic imag­ing exper­i­ments have demon­strat­ed that the rate of for­ma­tion of den­drit­ic spines tran­sient­ly under­goes a sig­nif­i­cant increase dur­ing learn­ing episodes in the adult ani­mal. More­over, new­ly formed spines have a high­er sur­vival prob­a­bil­i­ty than spines present pri­or to learn­ing. These obser­va­tions fit well with the idea that new mem­o­ries are encod­ed through synap­tic re-orga­ni­za­tion of neu­ronal net­works. Rather puz­zling is, on the oth­er hand, the obser­va­tion that spines are extreme­ly plas­tic also in the absence of explic­it learn­ing. In addi­tion, in-vit­ro stud­ies have report­ed sub­stan­tial net­work re-con­fig­u­ra­tion, even when the neur­al activ­i­ty is blocked. The con­sid­er­a­tion of the com­bined effects of spon­ta­neous re-wiring (spine turnover) and changes in effi­ca­cies (fluc­tu­a­tions in spine size), and of their time scales, leads to a some­how sur­pris­ing con­clu­sion: the learned synap­tic trace is extreme­ly short-lived (~ days) yet the behav­ioral expres­sion of the mem­o­ry can be sta­ble over years.

If mem­o­ries are encod­ed in the pat­tern and strengths of the con­nec­tions between neu­rons, how can they be sta­ble in face of the report­ed sub­stan­tial volatil­i­ty in synap­tic struc­tures? Could non-synap­tic plas­tic­i­ty mech­a­nisms play a far more impor­tant role in the for­ma­tion and con­sol­i­da­tion of mem­o­ries than cur­rent­ly thought? Are cur­rent com­pu­ta­tion­al mod­els of mem­o­ry for­ma­tion and reten­tion com­pat­i­ble with the above described exper­i­men­tal phe­nom­e­nol­o­gy or, instead, are they in need of sub­stan­tial amend­ments? This work­shop will bring togeth­er exper­i­men­tal­ists and the­o­reti­cians to address these ques­tions, while crit­i­cal­ly re-exam­in­ing suc­cess­es and prob­lems of the synap­tic trace the­o­ry of mem­o­ry.

 

Par­tic­i­pants:

Clau­dia Clopath (Impe­r­i­al Col­lege Lon­don), Dominique Debanne (U Aix-Mar­seille), Aline Desmedt (U Bor­deaux), Eric Hosy (IINS Bor­deaux), Yonatan Loewen­stein (Hebrew Uni­ver­si­ty), Jacques Micheau (U Bor­deaux), Simon Rumpel (Johannes Guten­berg Uni­ver­si­ty in Mainz)



Venue:

Con­fer­ence room of the Cen­ter for Neu­ro­physics, Phys­i­ol­o­gy & Pathol­o­gy
Paris Descartes Uni­ver­si­ty, 45 Rue des Saints Pères, Paris
(3rd floor, room H335)

 

Pro­gram:

09:00 – 09:30 Coffee & Croissants
09:30 – 10:30 Jacques Micheau (Bordeaux)
              Engram is coming back to the front of the scene: New data but old vista?
10:30 – 11:15 Aline Desmedt (Bordeaux)
              Switching from the search of the engram to the analysis of emergent memory – or – from a “neuronal syntax” to a
“neuronal semantic” 11:15 – 11:45 Coffee break 11:45 – 12:30 Simon Rumpel (Mainz) Dynamics of neuronal circuits in the mouse auditory cortex 12:30 – 13:15 Yonatan Loewenstein (Jerusalem) TBA 13:15 – 14:30 Lunch 14:30 – 15:15 Eric Hosy (Bordeaux) The use of super-resolution imaging techniques to revisit synaptic transmission 15:15 – 16:00 Dominique Debanne (Marseille) Long-term plasticity of intrinsic neuronal excitability: Learning rules and mechanisms 16:00 – 16:30 Coffee break 16:30 – 17:15 Claudia Clopath (London) Modeling synaptic plasticity and its implications in networks 17:15 – 17:45 Closing discussion