By combining a complex time-based learning task with advanced brain imaging, researchers were able to watch patterns of time cell activity become more complex as the mice learned. The researchers first set up a trial where learning the differences in the timing of events was critical. To get a reward, mice had to learn to distinguish between patterns of an odor stimulus that had variable timing, as if they were learning a very simple form of Morse code.
Before and after the mice learned, the researchers used cutting-edge microscopy to watch individual time cells fire in real time. At first, their time cells responded in the same way to every pattern of odor stimulus. But as they learned the differently timed patterns of stimulus, the mice developed different patterns of time cell activity for each pattern of events.
Notably, during trials that the mice got wrong, the researchers could see that their time cells had often fired in the wrong order, suggesting that the right sequence of time cell activity is critical for performing time-based tasks. “Time cells are supposed to be active at specific moments during the trial,” said Hyunwoo Lee, PhD, postdoctoral fellow in neurobiology in the Spencer Fox Eccles School of Medicine at the University of Utah and co-first author on the study. “But when the mice made mistakes, that selective activity became messy.”