Classical conditioning, such as the association between a tone and an odor, can be induced in sleeping humans. On page 493, de Lavilléon et al. report an attempt to create artificial memories in sleeping mice. The authors took advantage of the properties of hippocampal place cells, which are thought to encode specific locations in an animal's environment. Patterns of place cell activity generated during waking are replayed during subsequent sleep. This replay occurs during sharp wave ripples, which are an oscillatory pattern of activity thought to support memory consolidation. Pairing rewarding stimulation with replay of place cell activity, the authors showed that they could indeed induce artificial memories in sleeping mice.

The authors first showed that they could induce false memories in awake mice. They recorded from neurons in area CA1 of the hippocampus as mice explored an arena, analyzing spiking activity online to identify putative place cells. Using a brain-computer interface (BCI), they could pair activity of a particular place cell with stimulation of the medial forebrain bundle (MFB), which is known to be rewarding, with a very short latency (less than 2 ms). Such use of the BCI led mice to linger in the location encoded by the place cell paired with MFB stimulation, and their preference for this location remained even after the BCI was shut off.

In a second cohort of mice, the authors identified place cells while mice explored the arena, but they then allowed the animals to sleep. The BCI was then switched on, again pairing activity of a particular place cell with MFB stimulation, all while the mice slept. When mice were placed back in the arena after they woke up, mice went directly to the location encoded by the place cell whose activity was paired with MFB stimulation, and continued to display a preference for this location throughout the trial.

These results show that it is possible to induce new memories during sleep in mice. While previous studies in humans have shown that classical conditioning and implicit memories can be formed during sleep, this study goes a step further to show that an explicit memory leading to goal-directed behavior can be induced during sleep, and that this can be done using neural recordings and brain stimulation, bypassing sensory inputs. Further, because the memory induced by the authors here relied on activity of place cells that was uncoupled from the animal's actual position, this study provides the strongest evidence yet that place cells have a causal role in spatial memory and navigation.