Since their discovery in the 1990s, the brain cells which indicate the direction of the head have been called the “internal compass”. These cells are activated when an animal or human's head points in a certain direction and are thought to be important for spatial orientation and navigation.
A team of neuroscientists from the University of Tübingen has discovered that cells that orient the brain in mice do much more than that. They may be involved in the transmission of sensory and emotional information that is used to form memories of experiences, called “episodic memory”.
The results of the study were published in Nature Neuroscience.
Brain cells: this is how they modulate episodic memory
The brain cell research group was led by Professor Andrea Burgalossi of the Institute of Neurobiology and the Werner Reichardt Center for Integrative Neurosciences (CIN)
In the external world of human experience, the senses contribute together to the formation of memories. The visual stimulus of a picturesque landscape, the echo of a laugh, the warmth of a hug: all these sensory impressions are brought together in a region of the brain, the hippocampus. This processing is essential for transforming fleeting sensory perceptions into lasting memories.
“The hippocampus is a sort of neural curator that integrates information,” explains Burgalossi. “During an experience, a memory trace for that episode in our life is created in the hippocampus.”
To understand more precisely where sensory information enters the hippocampus from, the research team focused on one of its main input structures in the brain, the anterior thalamus.
“We have known for decades that this area is crucial for episodic memory. Patients with damage to this region of the brain suffer from memory loss,” says Dr. Patricia Preston-Ferrer, one of the lead authors of the study on brain cell function.
When scientists first recorded brain cell activity in the anterior thalamus of rodents in the 1990s, they found that cells that indicate the direction of the head were located there. “Previously, it was assumed that these only encode the direction of the animal's direction in its environment,” explains Preston-Ferrer. “But now our latest experiments show that this idea provides an incomplete picture.”
When the Tübingen research team recorded electrical activity in the mouse brain, they found that brain cells in the thalamus that indicate the direction of the head were activated when they exposed the mouse to sensory stimuli.
“When a sound was played, as well as when a tactile whisker was touched on the mouse's face, only the head direction brain cells were activated in a targeted and reliable manner and with a remarkably short delay,” explains the CIN researcher and co-author of the Giuseppe Balsamo studio. “We were surprised, since for decades it had been assumed that these neurons did not respond to sensory stimuli.”
The experiments revealed that in the anterior thalamus only head direction cells responded to sensory stimuli. “This tells us that brain cells must have a special function,” says Dr. Eduardo Blanco-Hernandez, a CIN researcher and co-author of the study.
“Their function must go beyond that of an internal compass.” Cells that control head direction also responded with increased activity to states of arousal, including social contact, such as meeting another mouse.
“It is known that attention and emotions have a great influence on the formation of memories and their quality. In such situations, we remember much more vividly than in a passive, uninvolved state,” says Blanco-Hernandez.
Overall, the new findings indicate that directional brain cells in the thalamus may constitute a key gateway for sensory, attention and arousal information entering the episodic memory system.
“To understand how a memory trace is formed, we need to know the pathways and nerve cells involved that transmit basic information to the hippocampus,” explains Burgalossi. “Based on our work, we believe that the inner compass represents a key node in this process.” Whether this node can be influenced, for example for therapeutic purposes, in order to better form and retrieve memories, will require further research.
Long-term memory of specific places is stored in the brain in so-called place cells. A team of neuroscientists led by Dr Andrea Burgalossi from the Werner Reichardt Center for Integrative Neuroscience (CIN) at the University of Tübingen has now reprogrammed such cells in free-roaming mice, sending electrical impulses directly to individual neurons.
After stimulation, these brain cells were reprogrammed so that their place-related activity shifted to the location where the stimulation was performed.
How do we know what happened to us yesterday or last year? How do we recognize the places we have been, the people we have met? Our sense of the past, which is always coupled with recognition of what is presently present, is probably the most important building block of our identity.
Plus, from not being late for work because we couldn't remember where the office was, to knowing who our friends and family are, long-term memory is what keeps us functional in our daily lives.
It is therefore not surprising that our brain relies on some very stable representations to form long-term memories. An example is memories of places we have seen. With each new place, our brain matches a subset of neurons in the hippocampus (a central brain area crucial for memory formation): they place brain cells.
The memory of a given environment is thought to be stored as a specific combination of place cell activity in the hippocampus: the place map. The place maps remain stable as long as we are in the same environment, but they rearrange their activity patterns in different places, creating a new place map for each environment.
To date, the mechanisms underlying this reorganization of cellular activity have remained largely unexplored. In 2016, neuroscientists from Tübingen, led by Dr. Andrea Burgalossi, had demonstrated that silent, dormant cells can be activated by electrical stimulation and become active cells in the rat brain.
Building on this work, the team continued to study the ways in which place cells form and have now presented evidence that brain place cells are not as stable as once thought: they can, in fact, even be reprogrammed.
The world-first implant uses juxtacellular recording and stimulation – a method in which a hair-thin electrode measures and induces tiny currents along individual brain cells – in live animals that roam freely in the laboratory arena.
With this setup, the researchers targeted individual cells in a mouse's brain and stimulated them in a different location from where they were originally active. In a significant number of cases, they found that the activity of place cells could be “reprogrammed”
The brain cells stopped firing in their original locations and became active in the area where the electrical stimulation was delivered. In other words, the reprogrammed place cells would henceforth become active whenever the mouse moved to the stimulus location, but would remain silent in the old location.
“We challenged the idea that place cells are stable entities. Even in the same environment we can reprogram individual neurons by stimulating them in specific points”, explains Andrea Burgalossi. “This discovery provides insight into the basic mechanisms that lead to the formation of new memories.” In the near future, scientists hope to be able to reprogram multiple neurons at once, in order to test the plasticity of geographic maps as a whole.
“So far we have reprogrammed individual neurons and it would be fascinating to find out what influence this has on place maps as a whole. We would really like to know what is the minimum number of brain cells that we need to reprogram to change an actual memory trace in the brain.”
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