Dr. Michael Zugaro

Our research is centered on neurophysiological mechanisms underlying cognitive functions, and our experimental model is spatial memory in rats. We record the activity of large neuronal ensembles as rats perform learning tasks, as well as during sleep. Our work combines several complementary approaches: animal behavior, electrophysiology, signal processing and data analysis.

In order to efficiently navigate in their environment, humans and animals benefit from strategies of varying complexity, ranging from stereotyped locomotor behavior to navigation using flexible and robust spatial representations. In rats, these representations emerge in at least three major neural systems: place and grid cells, that code for the position of the animal in its environment, and head direction cells, that code for its orientation. Eventually, studying these systems in rats will help us better understand human memory: indeed, recent work has started to provide evidence for similar mechanisms in rodents, monkeys and humans.

Our experimental approach consists in recording as well as dynamically perturbing the activity of brain structures involved in elaborating spatial representations in order to better understand how they operate. We are especially interested in the role of brain oscillations: in particular, the theta rhythm (~ 8 Hz) during exploration, and ripples (~ 200 Hz) during slow wave sleep. A major function of these oscillations would be to organize and coordinate the activity of anatomically distributed neuronal ensembles. This spatio-temporal organization could be instrumental for encoding as well as storing information.

When a rat explores its environment, different subsets of place cells activate in turn, forming neuronal sequences, as the rat walks along a given trajectory. However, while it takes the rat several seconds to walk along this trajectory, place cells activate much more quickly: a typical sequence lasts but a hundred milliseconds, i.e. one theta cycle. As a consequence, within a given theta cycle, place cells successively code for past, present and future locations. This may help plan trajectories. One aspect of our work consists in investigating the role of theta in the formation of place cells sequences.

Following exploration, during slow wave sleep, place cells spontaneously reactivate during ripples, and endogenously replay trajectories experienced during wake (as if the rat were dreaming that it explores its environment). It is generally believed that these reactivations could underlie a transfer of information to other cortical zones for long term storage. A second aspect of our work focuses on this reinforcement of memory during sleep. We have recently shown that the mere selective suppression of ripples and associated replay during sleep induces significant memory deficits. This result allowed us to confirm for the first time an influential theory of long-term memory formation, proposed some twenty years ago, but never validated before.