Summary: Researchers have discovered a new mechanism in the brain that improves memory formation while reducing energy consumption during sleep. The study reveals that this process occurs in the entorhinal cortex, a key area for learning and memory and the initial site of Alzheimer’s disease pathology.
The researchers used a new “mathematical microscope” to model how memories are consolidated in this region with minimal metabolic cost. This breakthrough could lead to better understanding and potential diagnoses of Alzheimer’s disease and related dementias.
Highlights:
- Innovative modeling approach: Researchers have developed a mathematical model that simplifies complex interactions in the brain to just two variables, making the study of memory formation easier.
- Energy-efficient memory processing: The study identifies a mechanism by which the brain can maintain memory states with less energy, a finding that contrasts with the high energy cost typically associated with active memory processes.
- Potential for early diagnosis: Understanding memory processing in the entorhinal cortex could provide early diagnostic clues for Alzheimer’s disease and other forms of dementia.
Source: UCLA
UCLA Health researchers have discovered a mechanism that creates memories while reducing metabolic costs, even during sleep. This efficient memory occurs in a part of the brain crucial for learning and memory, and where Alzheimer’s disease begins.
The discovery is published in the journal Natural communications.
Does this sound familiar: you go to the kitchen to get something, but when you get there, you forget what you wanted. It’s your failing working memory. Working memory is defined as remembering certain information for a short period of time while you do something else.
We use working memory almost all the time. Patients with Alzheimer’s disease and dementia have working memory deficits and this also manifests as mild cognitive impairment (MCI). Considerable effort has therefore been devoted to understanding the mechanisms by which the brain’s vast neural networks create working memory.
During working memory tasks, the outermost layer of the brain, known as the neocortex, sends sensory information to deeper regions of the brain, including a central region called the entorhinal cortex, which is crucial for training. souvenirs.
Neurons in the entorhinal cortex exhibit a complex set of responses, which have long intrigued scientists and resulted in the 2014 Nobel Prize in Medicine, but the mechanisms governing this complexity are unknown. The entorhinal cortex is where Alzheimer’s disease begins to form.
“It is therefore essential to understand what kind of magic happens in the cortico-entorhinal network, when the neocortex talks to the entorhinal cortex which transforms it into working memory.
“This could provide early diagnosis of Alzheimer’s disease and related dementia, as well as mild cognitive impairment,” said corresponding author Mayank Mehta, a neurophysicist and head of the WM Keck Neurophysics Center and Physics Center. of life at UCLA.
To solve this problem, Mehta and his co-authors designed a new approach: a “mathematical microscope.”
In the world of physics, mathematical models are commonly used, from Kepler to Newton and Einstein, to reveal amazing things we have never seen or even imagined, such as the inner workings of subatomic particles and the interior of a black hole.
Mathematical models are also used in brain science, but their predictions are not taken as seriously as in physics. The reason is that in physics, the predictions of mathematical theories are tested quantitatively and not just qualitatively.
Such quantitatively precise experimental tests of mathematical theories are generally considered infeasible in biology, because the brain is much more complex than the physical world.
Mathematical theories in physics are very simple, involving very few free parameters and therefore precise experimental tests. In contrast, the brain has billions of neurons and billions of connections, a mathematical nightmare, not to mention a very precise microscope.
“To address this seemingly impossible challenge of devising a simple theory that can still explain experimental data on in vivo memory dynamics with high precision, we hypothesized that cortico-entorhinal dialogue and magic “The memory loss would occur even when the subjects were asleep, or anesthetized,” said Dr. Krishna Choudhary, the lead author of the study.
“Just like a car behaves like a car when it’s idling or going 70 mph.”
The UCLA researchers then put forward another important hypothesis: the dynamics of the entire cortex and entorhinal cortex during sleep or anesthesia can be captured by just two neurons.
These hypotheses reduced the problem of interactions of billions of neurons to just two free variables: the strength of input from the neocortex to the entorhinal cortex and the strength of recurrent connections within the entorhinal cortex.
Even though this makes the problem mathematically solvable, it raises the obvious question: is it true?
“If we quantitatively test our theory on in vivo data, then it’s just interesting math games, not a solid understanding of memory-generating magic,” Mehta said.
The crucial experimental tests of this theory required sophisticated experiments by Dr. Thomas Hahn, a co-author who is now a professor at the University of Basel and a clinical psychologist.
“The entorhinal cortex is a complicated circuit. To truly test the theory, we needed experimental techniques that could not only measure neuronal activity with high precision, but also determine the precise anatomical identity of the neuron,” Hahn said.
Hahn and Dr. Sven Berberich, also a co-author, measured the membrane potential of identified entorhinal cortex neurons in vivo, using the whole-cell patch-clamp technique, and then used anatomical techniques to identify the neuron. Simultaneously, they measured activity in the parietal cortex, a part of the neocortex that sends information to the entorhinal cortex.
“Sophisticated mathematical theory and in vivo data are necessary and interesting, but we faced an additional challenge: how to apply this simple theory to complex neuronal data? » said Mehta.
“It required a long period of development to generate a ‘mathematical microscope’ that could directly reveal the inner workings of neurons as they make memory,” Choudhary said. “To our knowledge, this has never been done before. »
The authors observed that, like an ocean wave forming and then crashing onto a shore, signals from the neocortex oscillate between on and off states at regular intervals while a person or animal sleeps.
During this time, the entorhinal cortex acted like a swimmer in water that can move up when the wave forms and then move down when it recedes. The data showed it and the model captured it too.
But using this simple correspondence, the model then took on a life of its own and discovered a new type of memory state known as spontaneous persistent inactivity, Mehta said.
“It’s like a wave is coming and the entorhinal cortex is saying, ‘There’s no wave! I’m going to remember that recently there hasn’t been a wave so I’m going to ignore this current wave and not respond at all. This is persistent inactivity,” Mehta said.
“Alternatively, persistent activity occurs when the cortical wave disappears, but the entorhinal neurons remember that there was a wave very recently and continue moving forward.”
While many working memory theories had shown the presence of persistent activity, which the authors found, persistent inactivity was something the model predicted and had never been observed before.
“The interesting thing about persistent inactivity is that it requires almost no energy, unlike persistent activity, which requires a lot of energy,” Mehta said. “Better yet, the combination of persistent activity and inactivity more than doubles memory capacity while reducing memory. the metabolic energy cost by half.
“It all seemed too good to be true, which is why we really pushed our mathematical microscope to the extreme, into a regime where it was not designed to work,” Dr. Choudhary said. “If the microscope worked properly, it would continue to work perfectly even in unusual situations.”
“The mathematical microscope has made a dozen predictions, not only about the entorhinal but also about many other regions of the brain. To our surprise, the mathematical microscope worked every time,” Mehta continued.
“Such an almost perfect match between the predictions of a mathematical theory and experiments is unprecedented in neuroscience.
“This mathematical model perfectly suited to experiments is a new microscope,” Mehta continued.
“This reveals something that no existing microscope could see without it. No matter how many neurons you photographed, it wouldn’t have revealed any of this.
“In fact, metabolic deficiencies are a common feature of many memory disorders,” Mehta said. Mehta’s lab is now continuing this work to understand how complex working memory forms and what goes wrong in the entorhinal cortex during Alzheimer’s disease, dementia and other memory disorders.
About this research news on sleep and memory
Author: Will Houston
Source: UCLA
Contact: Will Houston – UCLA
Picture: Image is credited to Neuroscience News
Original research: Free access.
“Spontaneous persistent activity and inactivity in vivo reveal differential cortico-entorhinal functional connectivity” by Mayank Mehta et al. Natural communications
Abstract
Spontaneous persistent activity and inactivity in vivo reveal cortico-entorhinal differentials…
News Source : neurosciencenews.com
Gn Health
