he’d discovered was simply the smallest part of a memory, a tiny little memory trace. This response is now called long-term potentiation, meaning that a physical change occurs in some synapses in response to a recurring stimulus. At the same time as Lømo was making his discovery, neuroscientist Tim Bliss—a few thousand miles away from Oslo, at McGill University in Canada—had been looking for memory on a cellular level. What he lacked was the evidence that strengthened synapses were connected to memories. That is, until Lømo stumbled upon long-term potentiation! Bliss traveled to Oslo and the two did some experiments in 1968 and 1969, resulting in a scientific paper they published in 1973. Their paper presented a theory of how a memory is created on a micro level.
Almost nobody paid attention to the paper until twenty years later, because academia wasn’t ready for it. There was simply no context; no other studies had trodden even close to this particular corner of research. Since then, though, Bliss and Lømo’s paper has formed the basis for much of modern memory research. And now we know more: a memory consists of many of the connections they documented. One neuron can participate in many different memories. Memories are large networks of connections between neurons in the brain. When something becomes a memory, new links form—neurons either turn on or turn off, and either fire or don’t fire a signal in the brain, and in that way form a pattern.
Our memories cannot all remain in the hippocampus, so they spread out across the cortex. It takes time before a memory matures and all the complex connections it requires to store all that makes a memory—smells, tastes, sounds, moods, and images—are established in the brain.
“Sleep is needed for a memory to consolidate. We believe that while we’re asleep, we go through the events of the day in order for them to attach to the cortex. But when we are stressed, this doesn’t always happen. The neurons don’t fire in the same way. When I tried to re-create my experiment on other rabbits a couple of years later, it didn’t work,” Lømo recounts.
He’d been lucky the first time he experimented. His rabbit, despite its untimely end, had lived a happy life. The rabbits in the second experiment were stressed, so the neurons in their brains didn’t work as they should have. In other words, you must treat your test animals nicely if you want to learn from them. The same goes for humans: when we are stressed, we don’t retain memories as easily as when we are happy and relaxed.
At about the same time as Lømo’s discovery, there were other breakthroughs in the hunt for the memory trace. In 1971, John O’Keefe at University College London found cells in the hippocampus that remember certain locations. For example, there are some cells in the hippocampus that are active only when we sit on a certain chair, and not on another chair—even in the same room. It is evidently up to some cells (place cells) to remember where we have been at all times. But to remember a place in and of itself—is that a memory? The Norwegian neuropsychologists May-Britt Moser and Edvard Moser—together with John O’Keefe—were awarded the Nobel Prize in Physiology or Medicine in 2014 for their work on that very question. The two Norwegians received the prize because they decided to develop O’Keefe’s research further and look beyond the hippocampus. Their work examined the entorhinal cortex, which connects the hippocampus and the rest of the brain. The Mosers experimented with rats, which, when they were free to explore their environment, showed cells firing in exactly that part of the brain.
With tiny metal electrodes surgically inserted into their brains, these rats wandered around their cages. A single neuron in the entorhinal cortex didn’t react to just one place the rat had scurried to, like place cells, but to several places. Amazing, that what they were expecting to be place cells didn’t remember only one location but several locations in the same area! But when the Mosers marked the points in the cage where the cells had fired, they formed a perfect hexagon on their computer screen. The more the rats ran around in their cages and mazes, the more obvious it became; on the Mosers’ computer, a clear honeycomb pattern emerged. One cell, one hexagonal grid pattern. It was a coordinate system of the environment.
“At first, we thought there was something wrong with our equipment,” Edvard Moser says. “The pattern that emerged was too perfect to come out of something real.”
Each of these neurons makes its own grid, each slightly offset from that of the neighboring cells, so that all points in the environment are covered. Some grids are fine-meshed, while others react to points far away from each other, even farther than it is physically possible for the researchers to measure indoors. Without these grid cells, we are not able to understand or remember locations and where we are in relation to where we have been. We make these patterns wherever we go—wherever we stand, lie, or drive.
“We sent the rats into a ten-armed maze, and it turned out that they continued to make the grid pattern but also started a new one for each ‘arm.’ We believe that these patterns are patched together, so that the rats remember how to get through the maze,” Edvard Moser says.
Since then, other researchers have found the same result in patients undergoing epilepsy surgery. It was as anticipated: in humans, as in rats, all locations are stored in a hexagonal pattern. We are all bees! We all organize the world around us as a hexagonal grid.
“We believe that this was developed very early in the evolution of mammals,” Edvard Moser says. “And we believe that what we have discovered about grid cells is central for episodic memory. It is, after all, impossible to create memories without tying them to a place.”
Other researchers agree that place and grid cells play a special role in episodic memory. Some go so far as to say that this system in the hippocampus and the entorhinal cortex has become specialized to assign each memory its unique memory trace, as part of a unique memory network. Perhaps, at first, the sense of place was the primary task for the hippocampus and the entorhinal cortex. But as evolution proceeded, our memory maps were given a new function: to take our individual experiences and tie them together in a grid. Hexagonal maps of the environment became hexagonal-patterned fishnets of memories.
Recently, researchers in California have been able to demonstrate, in the hippocampi of mice, how memory networks link themselves to context-dependent memory. Like Terje Lømo, they made a window into the hippocampus, to the tiny little piece of it called cornu ammonis 1, Ammon’s horn. Looking at the hippocampus in cross-section, it looks like a goat’s horn, bent inward, into a spiral. Here, through the tiny window into the cradle of memory, the California researchers could see, under a slightly fancy microscope, how the neurons lit up when the mice were placed in different environments. They made three different cages, which would give rise to three different memories: a round cage, a triangular cage, and a square cage. The smell, texture, and other conditions also varied between the three cages. The crucial factor was how close in time the various experiences took place. Two groups of mice were compared. Half of the mice had a go at the triangular cage, and then directly afterward they were placed in the square cage. These mice got to experience two different cages in quick succession. The rest of the mice were placed in the round cage and then, seven days later, in the square cage. The second group of mice had two experiences—episodic memories—distinctly separated in time. When the researchers watched through the microscope while the mice were exploring the cages, they could see activity in the neurons in a defined area. Each of the three cages created a signature pattern of neuronal activity in the hippocampus, meaning distinct memories. The exciting part was that the experiences that took place close together in time led to activity in groups of neurons that overlapped. These two experiences hooked on to each other, not only in time but also in place, in the hippocampus of the mice. Meanwhile, when mice visited two cages a week apart, it was accompanied by activity in two separate groups of neurons in the hippocampus.
The researchers believe this happens because the activation of the one group of neurons causes other nearby neurons to become easier to activate. Everything links together in a network. The main point of Godden and Baddeley’s context-dependent memory experiment has, in this way, been demonstrated
