A key that tells the brain when to learn and when to remember

Summary: The study reveals a neural signal in the hippocampus that enables the brain to switch between learning and remembering modes.

source: Pasteur Institute

The memory system alternates between periods of learning and remembering. These two functions are controlled by different neural circuits.

Using an animal model, scientists from the Pasteur Institute recently identified a neural signal in the hippocampus, a brain region essential for the formation and retrieval of memories, which enables the brain to switch between memory and learning modes.

The results were published in the journal Nature Communications On July 15, 2022.

As we go about our lives, our brain constantly remembers information we learned in the past and uses it to make sense of the world in the present. However, we often encounter things and events that we have never experienced before, and then the brain needs to be ready to learn. It appears that these two primary functions of the brain’s memory system, learning and remembering, are constantly competing against each other.

“How the brain finds the balance between these two opposing processes is a question that has fascinated neuroscientists for a long time,” explains Christoph Schmidt-Heber, head of the Laboratory of Neural Circuits for Spatial Navigation and Memory at the Institut Pasteur.

Christoph Schmidt-Heber’s research group recently addressed this problem by designing an experiment in which mice explore virtual reality environments while recording their brains.

“We realized that the main obstacle to studying how the brain interacts with modernity is the physical reality itself!” Ruy Gómez-Ocádiz, a doctoral student in the lab and first author of the study, explains.

It is almost impossible to study the effect of absolute novelty on the brain in a traditional experiment, because one would immediately need to change everything the animal perceives.

“We could easily overcome this problem if we could only ‘teleport’ the mouse to a new room while we record its brain. This may sound like science fiction, but virtual reality technology has allowed us to do precisely that,” continues Roy Gomez-Ocadez.

Scientists have designed a video game in which mice learn to explore a virtual “world” and earn sugar rewards when they correctly follow simple game rules. While the mice played the video game, the researchers recorded the activity of neurons in the hippocampus, a brain region essential for forming and retrieving memories.

This indicates the dentate gyrus
Observation of the dentate gyrus in the hippocampus of a mouse model. Cell nuclei are stained with blue (DAPI). Record neuron activity shown in green (full of biocytin). Image width ~ 1 mm. Credit: Roy Gomez Ocadiz, Christoph Schmidt-Heber, Institut Pasteur

Using this innovative approach, they discovered an electrical signal in the hippocampus that appears at the exact moment when an animal teleports to a new virtual world. The signal is emitted by the granulosa cells and is triggered by the grandmother. It induces a transition from the state of neural memory to the state of learning.

Collaborating with physicists from École Normale Supérieure, PSL University, and CNRS, the scientists have developed a computational model that suggests how such a new signal could act as a switch to enable the brain to switch between memory and learning modes depending on the information in the environment.

Christoph Schmidt-Heber concludes, “The discovery of this new signal in the hippocampus provides exciting new clues to understanding how the brain finds the necessary balance between the formation of new memories and the retrieval of familiar memories.”

Financing: The study was funded by the above institutions, the European Research Council (ERC) and the French National Research Agency (ANR).

About this learning and memory research

author: Burlet Barendale Ann
source: Pasteur Institute
Contact: Burlet-Parendel Anne – Institut Pasteur
picture: The picture is attributed to Ruy Gómez-Ocádiz, Christoph Schmidt-Hieber, Institut Pasteur

original search: open access.
Synaptic signaling for new processing in the hippocampusWritten by Christoph Schmidt-Heber et al. Nature Communications

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Synaptic signaling for new processing in the hippocampus

Episodic memory formation and retrieval are complementary processes that rely on opposition to neural accounts in the hippocampus.

How this conflict is resolved in the hippocampal circuits is unclear.

To address this question, we obtained in vivo whole-cell patch-clamp recordings from dentate gyrus granule cells in head-fixed mice trained to explore and differentiate between familiar and novel virtual environments. We found that granulosa cells consistently exhibit small transient depolarization upon transition to a new environment.

This synaptic novelty signal is sensitive to local application of atropine, indicating that it is dependent on the metabolism-directed acetylcholine receptor.

A computational model suggests that the synaptic response to novelty may bias the activity of granule cell pools, which can drive downstream gravimetric networks to a new state, favoring the switch from retrieval to new memory formation when novelty is encountered.

Such a novelty-driven switch would enable flexible encoding of new memories while maintaining consistent retrieval of familiar memories.

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