Post by Kayla Simanek

What's the science?

Spatial exploration causes the sequential activation of specific neurons in the hippocampus (i.e. 'place cells') to track the ongoing location of the animal. The same neuronal sequences of activity are replayed at a faster rate during sleep for long-term memory commitment. How are these sequences initially memorized during exploration so that they can be replayed during sleep? Sequences are formed at two different time scales: a fast (theta) time scale and a slow, behavioral time scale. Theta sequences are ‘nested’ within slow behavioral sequences. The role of these different time scales in initial spatial memory formation during wakefulness had remained untested until now. This week in Science, Drieu and colleagues investigate whether theta sequences contribute to the initial formation of spatial memories.

How did they do it?

The authors put rats on a moving model train in a novel environment to test their ability to form long-term spatial memories. A treadmill on the model train was either turned off (passive travel) to disrupt theta sequences or turned on (active travel) to leave them intact. Active travel generates intact nested theta sequences while passive transportation is known to disrupt the precise timing of sequential place cell activation. Therefore, passive travel was expected to cause theta sequences to break-down in this study. Rats were tested in three sessions: passively, then actively, and passively again, alternated with periods of sleep, to determine if nested theta sequences were required for accurate replay of spatial memories during periods of sleep. The authors used a Bayesian reconstruction model to statistically analyze time scale patterns. Two quantifications were used: a combined value for trajectory score and slope to assess the quality of memory reconstruction, and a quadrant score to assess the direction of the reconstituted trajectory. To determine if neural sequences formed during initial spatial memorization were committed to long-term memory during sleep, the authors compared sleep sequences to those formed during wakefulness. Additionally, the sleep patterns of pre-active and post-active sessions were compared to confirm that sleep patterns observed were indeed reflective of those patterns formed during wakefulness and not from unrelated, pre-existing connectivity.

What did they find?

As hypothesized, the authors found that slow time scales were identical in all sessions and that genuine theta sequences were present only in active travel sessions. Active travel produced higher valued pairs of slopes and trajectory scores, consistent with greater quadrant scores, compared to passive travel, which confirmed that theta sequences were degraded in passive travel sessions and not active sessions. Neural sequences were found to be intact in sleep sessions after active travel (when theta sequences were previously formed in wakefulness) but not passive travel. This indicates a failure to commit short-term spatial memory to long-term after passive travel. Interestingly, theta sequences were perturbed to a lesser degree in the sleep session that followed the second round of passive travel compared to the first. This rules out the possibility that the emergence of theta sequences during active travel merely resulted from repeated experience. Finally, it shows that previously consolidated memory from active behavior can be undone by perturbation of theta sequences during passive travel.