When it comes to how we experience, interact and navigate our world, timing is everything. And new research in mice suggests that a specific set of cells is essential to how we learn complex behaviors that rely on timing.
The discovery by a team at the University of Utah in the US could eventually help detect the onset of neurodegenerative diseases that affect the perception of time, such as Alzheimer’s.
To create a memory for your personal archives, your brain must encode the timing and sequence 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 fire at specific moments during tasks, on a scale of seconds and minutes, a kind of organic internal metronome that helps us keep track of time in the moment.
Scientists suspect that this ‘timer’ can leave a mark on episodic memories, so that the ‘frames’ of our experience are reviewed in sequence, with a built-in rhythm. But to do so, these temporal cells will need learning dynamics that allow them to encode different temporal contexts.
We know that ‘spatial cells’ within the MTL can rearrange their ‘fields of fire’ according to spatial contexts as an animal moves through different and changing environments.
The researchers wanted to investigate whether temporal cells have a similar ability to ‘re-map’ in different temporal contexts. They combined a complex time-based learning task with brain imaging to look at temporal cell activity patterns.
If temporal cells are as flexible as their spatial cousins, the team hypothesized, then “(1) distinct sequences of temporal cells will become active as animals learn to identify a new temporal context, forming a unique map or ‘line time’ of any time context, and (2) such dynamics support the learning of time behavior.”
The first trial involved rats performing a task in which the timing of events was crucial, discriminating between a time-varying odor stimulus to obtain a reward.
The patterns in temporal cell activity were consistent regardless of the odor stimulus pattern, but became more complex as the rats learned, developing unique ‘time scales’ corresponding to each stimulus.
And when the mice tried it wrong, the researchers noticed, their temporal cells also fired in the wrong order.
“Time cells are supposed to be active at specific moments during the test,” says neurobiologist Hyunwoo Lee. “But when the mice made mistakes, that selective activity became erratic.”
When the researchers chemically blocked the MEC, disabling the mice’s timing cells, the animals were still able to perceive and predict the time of the event, but it became impossible for them to learn the time-based task all over again.
“Surprisingly, timing cells play a more complicated role than just keeping track of time,” says the study’s first author, neurobiologist Erin Bigus.
“The MEC is not acting as a really simple stopwatch that is needed to track time in any simple circumstance. Its role seems to be actually in learning these more complex temporal relationships.”
This research could lead to a better understanding of psychological conditions where people experience time very differently, such as Alzheimer’s, which we already know affects MEC early in its progression.
“We are interested in exploring whether complex behavioral timing tasks can be a useful way to detect the early onset of Alzheimer’s disease,” says 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 may help advance investigations there as well.
The researchers note that while they found that the MEC has a clear role in timing, there are other regions in the MTL, such as the hippocampus and lateral entorhinal cortex, that also encode timing.
“A clear future direction would include testing the necessity of other FTA regions,” the team wrote.
This research was published in Nature Neuroscience.