Focus on the "Cerebral Rhythms and Neural Coding of Memory" team

november 30, 2018

Since 2009, the Collège de France has pursued a proactive policy of hosting independent teams that benefit from its shared technical and scientific services and its exceptional multidisciplinary environment. This scheme, open to French and foreign researchers, helps consolidate Paris' attractiveness in the global geography of research. Twenty-two of these teams are currently housed at the Centre interdisciplinaire de recherche en biologie or at the Collège de France's chemistry and physics institutes.

Created in 2015, Michael Zugaro's "Cerebral Rhythms and Neural Coding of Memory" team (Collège de France, CNRS, INSERM, Université PSL) is one of them. Among its recent research results, it has lifted some of the veil that still surrounds brain activity during sleep. Although we know that certain neurons reactivate at this time to consolidate our memories, we didn't yet know how these cells could "remember" the order in which to switch on. Researchers have discovered that the reactivation of neurons during sleep is based on an activation that takes place during the course of the day: the "entangled" theta sequences. Their findings were published on November 9, 2018 in Science.

Many cognitive functions appear to be underpinned at the cerebral level by the formation of sequences of neuronal activity, i.e. by the successive activation of specific sets of neurons, in a very precise order. These functions range from vocalization in birds, to memory reactivation in primates, odor discrimination in locusts, and planning and decision-making in rats. Sequences of activity can occur more or less rapidly, from the slow time scale of behavior (that conditioned by perception or action), to the fast endogenous time scale (that conditioned by the intrinsic properties of the neural networks concerned). A particularly striking example is the hippocampus, whose place cells encode the position of animals in the environment. When an animal moves, place cells activate one after the other along the trajectory, forming sequences of activity on a behavioral timescale. Then, during sleep, these same sequences recur spontaneously, as if the animal were "dreaming" about the trajectories it has just travelled. These reactivations are highly accelerated, about twenty times faster, and help to reinforce memory during sleep. How can the sequential organization of place cells be maintained on such different timescales, manifested at totally separate moments in time, and in opposite brain states (wakefulness, sleep)?

A first possibility is that sequential information is directly recorded when neurons activate one after the other on the time scale of behavior. A second, more enigmatic possibility involves the remarkable property of the hippocampus to generate entangled sequences of activity, i.e. a deeply intertwined mixture of slow and fast sequences. This actually happens during exploration: even as the place cells activate slowly one after the other, the hippocampal network also generates sequences of activity on the time scale of a brain oscillation called "theta", whose cycles last a mere 150 ms. This enables the locus cells to activate repeatedly, one after the other, very rapidly, as if at any instant they represented the entire trajectory in progress. Thanks to their high speed, these entangled sequences would enable the locus cells to strengthen their connections, and thus memorize their activation sequence. But is this really the mechanism that enables the hippocampus to memorize trajectories, or just a simple epiphenomenon, however striking?

To answer this question, Michael Zugaro's team recorded sequences of hippocampal activity in rats during environmental exploration and sleep. They developed an ingenious protocol which enabled them to rapidly and selectively disrupt the entangled sequences of activity, without affecting the slow sequences. Thus, the place cells were always activated one after the other as the rats moved through the environment (on the behavioral time scale), but the entangled sequences (on the theta rhythm time scale) could be suppressed at will. The "Cerebral Rhythms and Neural Coding of Memory" team found that disruption of the entangled sequences resulted in a total absence of reactivations during the following sleep period, reactivations which normally enable memory consolidation. So it is indeed thanks to its astonishing ability to produce both fast and slow sequences at the same time, thanks to this entanglement of time scales, that the hippocampus can initially store memories that will later be reinforced during sleep to enable long-term memorization.