The “Learning Layer” of the Cortex

Post by Anastasia Sares

What's the science?

The hippocampus is known to play a central role in learning and memory. The brain areas immediately surrounding the hippocampus, like the perirhinal cortex, are also involved. However, mature memories don't rely on the hippocampus —they are stored in a distributed way throughout the cortex (outer layer of the brain). The exact locations and mechanisms for memory storage in the cortex have been a long-standing mystery since the early 20th century. Nevertheless, it is generally assumed that auditory memories will be stored predominantly in the auditory cortex, or a movement memory will be stored in the motor cortex, and so on. The exact location of memories in the cortex is difficult to pin down.

This week in Science, Doron and colleagues demonstrate a new way of locating memory in the cortex. Instead of treating the cortex like a 2D map, they looked at the brain in 3D space, like a forest of trees, and showed that memories are actually stored in a specific sublayer of the cortex, layer 1, atop the forest. They were able to demonstrate that messages crucial for long-term memory formation are sent from the hippocampus to layer 1.

How did they do it?

The authors first traced the paths of neurons from the perirhinal cortex, showing that neurons starting here signal to other parts of the cortex, in layer 1. Next, they taught mice and rats to respond to a small electrical stimulation applied directly to their brain, specifically, the somatosensory cortex (the part of the cortex that processes touch information from the body). When they licked a small apparatus right after receiving stimulation, the animals were rewarded. With this design, the authors could pinpoint exactly where in the cortex the long-term memory would be made: it would be in the same place as the stimulation. In some animals, the authors disrupted the connection between perirhinal cells and layer 1 of the somatosensory cortex, either during or after training on the task. Other animals' connections were left intact as a control.

What did they find?

Compared to the controls, animals with disrupted connections between the perirhinal cortex and layer 1 of somatosensory cortex showed impaired learning, but only if the disruption happened during the learning phase. Expert animals were not affected by this disruption, since their memory for the task had already been formed. For all of the animals, the neurons in the perirhinal cortex fired in response to the stimulus when the animal responded correctly. However, activity in the somatosensory cortex was less robust in the animals whose connections were disrupted. The authors reasoned that the real targets for these signals from perirhinal cells were the large pyramidal neurons in layer 5 of the cortex because their dendrites stretch all the way up to layer 1, where they should capture the signal from the perirhinal cells. In the mice and rats that learned normally, these layer 5 cells changed their firing pattern after a correct response, similar to the perirhinal cells. In the animals with a disrupted layer 1 connection, layer 5 cells were much less responsive.

What's the impact?

This study highlights the central role of layer 1 of the cortex in storing memory. Human memory is extremely complex, and we are growing in our understanding of it every year. Unlocking the mechanisms behind memory formation will aid in the fight against human diseases like Alzheimer's, and may also inform the way we make artificial neural networks, helping machines to learn in a more biological way.

Doron et al.Perirhinal input to neocortical layer 1 controls learning. Science (2020). Access the original scientific publication here.