Norwegian University of Science and Technology researchers have discovered a pattern of brain activity that can be used to build sequential experiences. The finding of a rigid sequence pattern in the brain provides new insights into how we organize experiences into a temporal order.
“I believe we have found one of the brain’s prototypes for building sequences,”
said Professor Edvard Moser of NTNU’s Kavli Institute for Systems Neuroscience. He refers to the activity pattern as a fundamental algorithm that is inherent in the brain and unaffected by experience.
Videos, Not Shapshots
The ability to organize components into sequences is a basic biological capability that is required for human survival. We couldn’t communicate, keep track of time, locate our route, or even remember what we were doing if we didn’t have it.
The world would cease to present itself to us in meaningful experiences, as every event would be fragmented into an erratic series of random happenings.
You have probably heard someone refer to memories as snapshots. But Professor Moser says that’s not a really accurate description. Instead, he suggested, it is more helpful to think of memories as videos.
“All your experiences in the world extend over time. One thing happens, then another thing, then a third,”
says Professor May-Britt Moser.
The human brain exhibits an exceptional capability of conceptualizing and arranging particular occurrences in a sequential fashion, as well as connecting them as significant experiences.
Timescale Mismatch
This sequence-building action occurs on the timescale that you engage with the situation. When you recollect this experience, the process of mentally reliving the sequence of events takes time as well.
“How is the brain able to generate and store all these unique and lengthy sequences of information on the fly? There has to exist a foundational mechanism for sequence formation there,”
said Edvard Moser.
“There is a mismatch in neuroscience between the timescales at which brain activity is typically studied, in the millisecond regime, and the timescales at which many of our most important brain functions occur, in the tens of seconds to several minutes range,”
said Soledad Gonzalo Cogno, Kavli Research Group Leader and first author of the paper, expanding on the motivation behind this study. The team set out to locate this underlying mechanism for sequence generation, which happens on very slow timescales, just like most of our brain does.
Medial Entorhinal Cortex
The Kavli researchers looked at the medial entorhinal cortex (MEC) to find out how neurons work together at the very slow timescales at which many of our brain functions happen. The MEC is a part of the brain that supports functions that depend on making connections between events, like navigation and episodic memory, which happen very slowly.
The enormous amount of information about the outside world being processed in the brain at any given time made the pursuit difficult. Any baseline signal generated by organized and recurrent neural algorithms risks being drowned out by the “noise” of incoming experience.
To get around this, the researchers created an experimental environment that was almost devoid of sensory inputs. They let a mouse run in complete darkness, with no task to complete and no reward to earn. The mouse could run or rest as it pleased for as long as the session lasted.
At the same time, the researchers observed what was happening in the mouse’s brain’s entorhinal cortex while its orchestra of nerve cells remained silent.
Rhythms in a Symphony
Soledad Gonzalo Cogno pointed to a zebra-striped figure before her and said “This is what we found.”
The pattern is made up of thousands of dots clustered together. Each dot is a neural signal.
The sequences are ultra-slow, meaning that it takes two minutes for the wave to travel through the neural network, before the whole process repeats again, sometimes for as long as the duration of the test session, over periods of up to an hour.
The figure shows several hundred mouse entorhinal cortex neurons oscillating at ultra-slow frequencies, spanning time windows ranging from tens of seconds to several minutes.
The dynamic that excited the researchers, even more, is that as each cell oscillates, the cells also organize themselves into sequences, with cell A firing before cell B, cell B firing before cell C, and so on, until they have completed a full loop and return to cell A, where the cycle repeats.
We can see that the neural activity moves through all the cells from bottom to top along the Y-axis as time progresses along the X-axis. The clustering tells us that the activity is coordinated as waves running through the network, like rhythms in a symphony.
Sequential Structure Template
This highly structured activity overlaps with the timescale of events that we encode into our memories, and it serves as the ideal template for constructing the sequential structure that serves as the foundation of episodic memories.
These coordinated activity waves did not flow directly from one end of the brain tissue to the other. Instead, the waves move along the network’s narrow synaptic connections between cells that communicate with one another.
Cells can talk to other cells far away and to their nearest neighbors. The anatomical tangle makes it difficult to see coordinated activity with the naked eye without first locating the cells from the raster plot.
Zebra-striped Raster Plot
The zebra-striped raster plot shows the slow waves of activity through the whole network over a period of time.
“If you fold the raster plot into a tube so that the top and the bottom of the figure overlap, you will see that the diagonal stripes connect to form a coherent spiral. The spiral represents the network activity over time,”
explained May-Britt Moser.
You will see a ring if you rotate the spiral by 90 degrees. All the cells in the network have their set time to fire, distributed across the surface of this ring. The signal travels through the entire ring structure before returning to the same cell.
“This ring is a signature for coordination patterns in the form of repetitive sequences, which is what we found in the MEC. Other brain areas have different coordination patterns,”
said Soledad Gonzalo Cogno.
Your brain may already be equipped with this ring before you experience anything in this world. It is acquired through evolution and may be specified in our genes.
“What excites me most about this discovery is the prospect that these sequences may open up for new ways of understanding the brain. The discoveries that follow may challenge the way we think about coordination throughout the brain. Cells that are so different still seem to be coordinated and work together on different timescales,”
said Gonzalo Cogno.
Abstract
The medial entorhinal cortex (MEC) hosts many of the brain’s circuit elements for spatial navigation and episodic memory, operations that require neural activity to be organized across long durations of experience1. Whereas location is known to be encoded by spatially tuned cell types in this brain region2,3, little is known about how the activity of entorhinal cells is tied together over time at behaviourally relevant time scales, in the second-to-minute regime. Here we show that MEC neuronal activity has the capacity to be organized into ultraslow oscillations, with periods ranging from tens of seconds to minutes. During these oscillations, the activity is further organized into periodic sequences. Oscillatory sequences manifested while mice ran at free pace on a rotating wheel in darkness, with no change in location or running direction and no scheduled rewards. The sequences involved nearly the entire cell population, and transcended epochs of immobility. Similar sequences were not observed in neighbouring parasubiculum or in visual cortex. Ultraslow oscillatory sequences in MEC may have the potential to couple neurons and circuits across extended time scales and serve as a template for new sequence formation during navigation and episodic memory formation.
Reference:
- Gonzalo Cogno, S., Obenhaus, H.A., Lautrup, A. et al. Minute-scale oscillatory sequences in medial entorhinal cortex. Nature (2023). Doi: 10.1038/s41586-023-06864-1