Summary: New research reveals that the brain’s “time cells,” crucial for learning complex behaviors requiring precise timing, are not simple stopwatches. These cells adapt their firing patterns as mice learn to distinguish differently timed events, suggesting a more complex role in processing temporal information. This discovery could contribute to the early detection of neurodegenerative diseases such as Alzheimer’s disease.
Highlights:
- Temporal cells fire in sequence to map short periods of time.
- These cells change their activity patterns as mice learn complex time-based tasks.
- Temporal cells are essential for learning but not for the simple perception of time.
Source: University of Utah
The notion of time is fundamental to the way we understand, remember and interact with the world. Tasks ranging from holding a conversation to driving a car require us to remember and perceive how long things take – a complex but largely unconscious calculation that is constantly happening beneath the surface of our thoughts.
Now, researchers at University of Utah Health have discovered that in mice, a specific population of “time cells” is essential for learning complex behaviors where timing is essential. Like the second hand on a clock, time cells fire in sequence to map short periods of time.
But researchers have discovered that temporal cells are more than just a clock: As animals learn to distinguish between differently timed events, the temporal cells’ pattern of activity changes to represent each pattern of events differently. This discovery could ultimately contribute to the early detection of neurodegenerative diseases, such as Alzheimer’s disease, which affect time perception.
The new study is published in Natural neuroscience.
Mouse code
By combining a complex time-based learning task with advanced brain imaging, the researchers were able to observe that the activity patterns of temporal cells became more complex as the mice learned. The researchers first set up a trial in which it was essential to learn about differences in the timing of events. To get a reward, the mice had to learn to distinguish patterns of a variable-timing olfactory stimulus, 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 observe the firing of individual temporal cells in real time. At first, their temporal cells responded the same way to each type of olfactory stimulus. But as they learned the different stimulus patterns, the mice developed different patterns of temporal cell activity for each pattern of events.
Notably, on trials where the mice made a mistake, the researchers found that their temporal cells often fired in the wrong order, suggesting that the correct sequence of temporal cell activity is essential for performing tasks. temporal.
“Temporal cells are thought to be active at specific times during the trial,” said Hyunwoo Lee, PhD, a postdoctoral researcher in neurobiology at the University of Utah Spencer Fox Eccles School of Medicine and co-first author. of the study.
“But when the mice made mistakes, this selective activity became disordered.”
Not just a stopwatch
Surprisingly, temporal cells play a more complex role than just tracking time, said Erin Bigus, a graduate research assistant in neurobiology and co-first author of the study.
When the researchers temporarily blocked activity in the region of the brain that contains temporal cells, the medial entorhinal cortex (MEC), the mice could still perceive and even anticipate the timing of events. But they couldn’t learn complex time-related tasks from scratch.
“The MEC does not act as a simple stopwatch needed to track time in simple circumstances,” Bigus said. “Its role seems to be to actually learn these more complex temporal relationships.”
Intriguingly, previous research on the MEC has found that it is also involved in learning spatial information and constructing “mental maps.” In the new study, the researchers noticed that the patterns of brain activity that occur when learning temporal tasks have some similarities to previously observed patterns involved in spatial learning; some aspects of both models persist even when an animal is not actively learning.
Although more research is needed, these results suggest that the brain may process space and time in fundamentally similar ways, according to the researchers.
“We think the entorhinal cortex might serve a dual purpose, acting as both an odometer to track distance and a clock to track elapsed time,” said James Heys, PhD, assistant professor of neurobiology and senior author of the study.
“These are the first areas of the brain affected by neurodegenerative diseases such as Alzheimer’s disease. We want to explore whether complex behavioral tasks could be a useful way to detect early onset of Alzheimer’s disease. –James Heys
Learning how the brain processes time could eventually help in the detection of neurodegenerative diseases such as Alzheimer’s, researchers say. The ECM is one of the first areas of the brain affected by Alzheimer’s disease, suggesting that complex timing tasks could potentially be a way to detect the disease at an early stage.
Funding: Support was provided by the Whitehall Foundation, the Brain and Behavior Research Foundation, the National Institutes of Health, and the National Science Foundation.
About this news on research in neuroscience and learning
Author: Sophie Friesen
Source: University of Utah
Contact: Sophia Friesen – University of Utah
Picture: Image is credited to Neuroscience News
Original research: Closed access.
“The medial entorhinal cortex facilitates learning of context-dependent interval timing behavior” by Hyunwoo Lee et al. Natural neuroscience
Abstract
Medial entorhinal cortex facilitates learning of context-dependent interval timing behavior
Episodic memory requires the encoding of the temporal structure of experience and relies on brain circuits in the medial temporal lobe, including the medial entorhinal cortex (MEC). Recent studies have identified MEC “temporal cells,” which fire at specific times during interval timing tasks, collectively spanning the entire timing period.
It has been hypothesized that temporal MEC cells might provide the temporal information necessary for episodic memories, but it remains unclear whether they display the learning dynamics required to encode different temporal contexts. To explore this, we developed a new behavioral paradigm requiring mice to discriminate temporal contexts.
In combination with cellular resolution calcium imaging methods, we found that temporal MEC cells display context-dependent neuronal activity that emerges with task learning.
Through chemogenetic inactivation, we discovered that MEC activity is necessary for learning context-dependent interval timing behavior. Finally, we found evidence for a common circuit mechanism that could drive the sequential activity of temporal cells and spatially selective neurons in the MEC.
Our work suggests that clock firing of MEC temporal cells can be modulated by learning, thereby enabling the tracking of diverse temporal structures that emerge from experience.