When it comes to how we experience, interact with, and navigate our world, timing is everything. And new research in mice suggests that a specific set of cells is fundamental to how we learn complex behaviors that rely on timing.
The discovery by a team from the University of Utah in the US could eventually help detect neurodegenerative diseases that affect time perception, such as Alzheimer’s disease.
To create a memory for your own personal archives, your brain must encode the timing and order of events as you experience them. It creates this timeline using circuits in the medial temporal lobe (MTL), one of which is the medial entorhinal cortex (MEC).
This MEC circuit has ‘time cells’ that activate at specific times during tasks, on a scale of seconds and minutes. It’s a kind of organic internal metronome that helps us keep track of the time at that moment.
Scientists suspect that this ‘timer’ puts its stamp on episodic memories, so that the ‘frames’ of our experience are played back in order, with a built-in rhythm. But to do that, these time cells would need learning dynamics that allow them to encode different temporal contexts.
We know that ‘spatial cells’ within the MTL can reorganize their ‘firing fields’ based on spatial contexts as an animal moves through different and changing environments.
The researchers wanted to investigate whether time cells have a similar ability to ‘remap’ in different temporal contexts. They combined a complex time-based learning task with brain imaging to observe patterns of time cell activity.
If time cells are as flexible as their spatial cousins, the team hypothesized, then “(1) different sets of time cells will become active as animals learn to identify a new temporal context, forming a unique map or ‘timeline’ of each context, and (2) such dynamics support the learning of timing behavior.”
On the first trial, the mice had to complete a task where the timing of events was crucial, distinguishing between an odor stimulus with variable timing, to obtain a reward.
The patterns of time cell activity were consistent regardless of the odor stimulus pattern, but became more complex as the mice learned, developing unique ‘time scales’ corresponding to each stimulus.
And when the mice performed the experiment incorrectly, the researchers noticed that their time cells also went off in the wrong order.
“Time cells should be active at specific times during the experiment,” says neurobiologist Hyunwoo Lee. “But when the mice made mistakes, that selective activity became messy.”
When the researchers chemically blocked the MEC, thereby disabling the mice’s time cells, the animals could still perceive and predict the timing of events, but it became impossible for them to relearn the time-based task from scratch.
“Surprisingly, time cells play a more complex role than just keeping track of time,” said the study’s lead author, neurobiologist Erin Bigus.
“The MEC does not behave like a very simple stopwatch that is needed to keep track of time in simple circumstances. Its role seems to be in actually learning these more complex temporal relationships.”
This research could lead to a better understanding of psychological conditions in which people experience time very differently, such as Alzheimer’s disease, which we already know affects the MEC early in its progression.
“We are interested in investigating whether complex timing behavioral tasks could be a useful way to detect early onset Alzheimer’s disease,” said the study’s senior author, neurobiologist James Heys.
There is also growing interest in how ‘time blindness’ – a symptom of ADHD and autism – arises. Understanding how time is mapped and recorded in the brain could also help with research there.
The researchers noted that while the MEC plays a clear role in timing, there are other areas in the MTL, such as the hippocampus and lateral entorhinal cortex, that also code time.
“A clear future direction will involve testing the need for other MTL regions,” the team writes.
This research was published in Nature Neuroscience.