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大腦神經學：一般研究 – 開欄文
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2023/11/03 18:50 瀏覽2,567 ｜回應12｜推薦1 |
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我對大腦神經學的興趣始自上一世紀80年代。
我最早的求知動機在於回答：「行為是否需要準則」和(如果需要)「行為準則是什麼」這兩個問題。後來逐漸領悟到：這兩個問題其實是「決策判定」的問題。做為工程師，我自然了解「決策」的基礎在「知識」。從而，我的讀書範圍從倫理學和社會學擴充到「認識論」。1982前後我讀了第一本介紹「認知科學」的書。自此，大腦神經學成為我主要的閱讀對象。從2000年以後，我立論的基本假設都包含我對它的粗淺了解。《唯物人文觀》(2006)則是我第一次嘗試整合我對大腦神經學與人文/社會科學兩個領域的了解。
最近我起了整合本城市討論/報導過各個重要議題的念頭；大腦神經學自然在列。等我完成手頭兩篇討論「文化」的文章後，我會開始討論「意識」。
本文於 2024/04/14 00:43 修改第 3 次
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昏過去的原因 ------ Miryam Naddaf
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2023/11/03 23:07 推薦1 |
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我今年8月身體微恙。有一天半夜起來如廁時昏了過去；但沒多長就醒過來。走了幾步後又昏了過去；也是沒多長就醒過來。兩次症狀和下文描述的一樣；同樣情況十幾、二十年前也發生過一次。
十月中我到心臟科做了整套檢查，醫生說我的心臟沒有問題。前兩天剛好看到這篇文章，和各位分享。如果碰到類似狀況，應該盡快做檢查；但不必驚慌或自己嚇自己。
What causes fainting? Scientists finally have an answer
Mouse experiments reveal the brain-heart connections that cause us to rapidly lose consciousness — and wake up moments later.
Miryam Naddaf, 11/01/23
Whether as a result of heat, hunger, standing for too long, or merely at the sight of blood or needles, 40% of people faint at least once in their lifetime.
But exactly what causes these brief losses of consciousness — which researchers call ‘syncope’ — has remained a mystery for cardiologists and neuroscientists for a long time.
Now, researchers have discovered a neural pathway, which involves a previously undiscovered group of sensory neurons that connect the heart to the brainstem. The study, published in Nature on 1 November1, shows that activating these neurons made mice became immobile almost immediately while displaying symptoms such as rapid pupil dilation and the classic eye-roll observed during human syncope.
The authors suggest that this neural pathway holds the key to understanding fainting, beyond the long-standing observation that it results from reduced blood flow in the brain. “There is blood flow reduction, but at the same time there are dedicated circuits in the brain which manipulate this,” says study co-author Vineet Augustine, a neuroscientist at the University of California, San Diego.
“The study of these pathways could inspire new treatment approaches for cardiac causes of syncope,” says Kalyanam Shivkumar, a cardiologist at the University of California, Los Angeles.
Novel neurons
The mechanisms that control how and why people faint have long puzzled scientists, partly because researchers tend to focus on studying either the heart or the brain in isolation. But the authors of the study developed novel tools to show how these two systems interact.
Using single-cell RNA sequencing analysis of the nodose ganglia, an area in the vagus nerve (which connects the brain to several organs, including the heart), the team identified a group of sensory neurons that express a type of receptor involved in the contraction of small muscles within blood vessels that causes them to constrict.
These neurons, called NPY2R VSNs, are distinct from other branches of the vagus nerve that connect to the lungs or the gut. They instead form branches within the lower,muscular parts of the heart, the ventricles, and connect to a distinct area in the brainstem called area postrema.
Using a new technique that combines high-resolution ultrasound imaging with optogenetics — a way of controlling neuron activity using light — the researchers stimulated the NPY2R VSNs in mice while monitoring their heart rate, blood pressure, respiration and eye movements. This approach allowed the team to manipulate specific neurons and visualise the heart in real time. “This was not possible before, because you needed to figure out the identity of these neurons,” says Augustine.
When the NPY2R VSNs were activated, mice that had been freely moving around fainted with a few seconds. While passed out, the mice displayed similar symptoms to humans during syncope, including rapid pupil dilation and eyes rolling back in their sockets, as well as reduced heart rate, blood pressure, breathing rate and blood flow to the brain.
“We now know that there are receptors in the heart that when made to fire, will shut down the heart,” says Jan Gert van Dijk, clinical neurologist at Leiden University Medical Centre in the Netherlands.
In humans, syncope is usually followed by a rapid recovery. “Neurons in the brain are very much like extremely spoiled children. They need oxygen and they need sugar, and they need them now,” says Dijk. “They stop working very quickly if you derive them off oxygen or glucose.”
These nerve cells begin to die after about 2 to 5 minutes without oxygen, but syncope typically lasts only 20 to 40 seconds. “If you add oxygen again, they'll simply resume their work and do so just as quickly,” says Dijk.
Brain activity
To better understand what happens inside the brain during syncope, the researchers recorded the activity of thousands of neurons from various brain regions in mice using electrodes. They found that activity decreased in all areas of the brain except one specific region in the hypothalamus known as PVC.
When the authors inhibited/blocked the activity of PVC, the mice experienced longer fainting episodes, while its stimulation caused the animals to wake up and start moving again. The team suggests that a coordinated neural network that includes NPY2R VSNs and PVC regulates fainting and the rapid recovery that follows.
“Coming from a clinical standpoint, this is all very exciting,” says Richard Sutton, clinical cardiologist at Imperial College London. The discovery of NPY2R VSNs “doesn't answer all questions immediately”, he adds, “but I think it could answer with future research almost everything.”
For “questions that cardiologists have been asking for decades, now you can bring in a neuroscience perspective and really see how the nervous system controls the heart”, says Augustine.
The next big question is studying how these neurons are triggered, says Dijk. “It's been one of the biggest riddles of my entire career.”
doi: https://doi.org/10.1038/d41586-023-03450-3
References
Lovelace, J. W. et al. Nature https://doi.org/10.1038/s41586-023-06680-7 (2023).
本文於 2023/11/03 23:08 修改第 2 次
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最新的大腦結構圖 -- Gemma Conroy
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2023/11/03 18:54 推薦1 |
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This is the largest map of the human brain ever made
Researchers catalogue more than 3,000 different types of cell in our most complex organ.
Gemma Conroy, 10/12/23
Researchers have created the largest atlas of human brain cells so far, revealing more than 3,000 cell types — many of which are new to science. The work, published in a package of 21 papers today in Science, Science Advances and Science Translational Medicine, will aid the study of diseases, cognition and what makes us human, among other things, say the authors.
The enormous cell atlas offers a detailed snapshot of the most complex known organ. “It’s highly significant,” says Anthony Hannan, a neuroscientist at the Florey Institute of Neuroscience and Mental Health in Melbourne, Australia. Researchers have previously mapped the human brain using techniques such as magnetic resonance imaging, but this is the first atlas of the whole human brain at the single-cell level, showing its intricate molecular interactions, adds Hannan. “These types of atlases really are laying the groundwork for a much better understanding of the human brain.”
The research is part of the US National Institutes of Health’s Brain Research through Advancing Innovative Neurotechnologies Initiative — Cell Census Network (BICCN), a collaboration between hundreds of scientists. The programme’s goals include cataloguing brain cell types across humans, non-human primates and mice to improve understanding of the cellular mechanisms behind poorly understood brain disorders. The data from the 21 studies have been made publicly available on the Neuroscience Multi-omic Archive online repository.
Cellular menagerie
Kimberly Siletti, a neuroscientist now at the University Medical Center Utrecht in the Netherlands, and her team laid the cornerstone for the atlas by sequencing the RNA of more than 3 million individual cells from 106 locations covering the entire human brain, using tissue samples from three deceased male donors1. They also included one motor cortex dissection from a female donor that had been used in previous studies. Their analysis documented 461 broad categories of brain cell that included more than 3,000 subtypes. “I was surprised at how many different cell types there were,” says Siletti.
Neurons — cells in the brain and nervous system that send and receive signals — varied widely in different parts of the brain, suggesting different functions and developmental histories. The mix of neurons and other cell types also differed across each region; some cells were only found in specific locations. The brainstem — a relatively under-studied structure connecting the brain to the spinal cord — harboured a particularly high number of neuron types, says study co-author Sten Linnarsson, a molecular systems biologist at the Karolinska Institute in Stockholm, Sweden. “One of the big surprises here is how incredibly complex the brainstem is.”
Other studies drilled into the mechanisms of gene regulation and expression in different cells. Joseph Ecker, a molecular biologist at the Salk Institute for Biological Studies in La Jolla, California, and his colleagues investigated the brain through an epigenetic lens using tissue samples from the same three donors2. They analysed chemical markers that switch genes on or off in more than 500,000 individual cells. The various molecules that acted as switches enabled the team to identify nearly 200 brain cell types. Even the same gene in the same type of cell could have different characteristics across the brain. One gene was turned on with one switch at the front of the brain and with another at the back. “There are remarkable regional differences,” says study co-author Wei Tian, a computational biologist at the Salk Institute.
Pinpointing the switches that activate or block gene expression in brain cells could be useful for diagnosing brain disorders and developing tailored treatments, says Ecker. “That’s another tool that comes out of the toolbox we’re building,” he says.
Disease risk
Improving understanding of how genetic switches might contribute to disease risk was also a focus for Bing Ren, a molecular biologist at the University of California, San Diego, and his team3. They analysed how more than one million brain cells from the three donors access and use genetic information. The researchers uncovered links between certain brain cell types and neuropsychiatric disorders, including bipolar disorder, depression and schizophrenia.
Ren and his colleagues used the cell-type data to predict how the genetic switches influence gene regulation and increase the risk of neurological diseases. For instance, in cells called microglia , which clear away dead or damaged cells, the presence of some genetic switches was strongly linked to risks of Alzheimer's disease. Such findings can be used to test whether particular genes or faulty switches contribute directly to the onset of disease. “This is made possible because we have — for the first time — delineated the genetic switches for hundreds of different cell types,” says Ren.
The next step for the BICCN team is to sequence more cells from all parts of the brain, says Ren. The researchers will also work with more tissue samples to build a picture of how the human brain can vary across populations and age groups. “This is only the beginning,” says Ren.
doi: https://doi.org/10.1038/d41586-023-03192-2
References
Siletti, K. et al. Science 382, eadd7046 (2023).
Article Google Scholar
Tian, W. et al. Science 382, eadf5357 (2023).
Article Google Scholar
Li, Y. E. et al. Science 382, eadf7044 (2023).
Article Google Scholar
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本文於 2023/11/03 18:54 修改第 1 次
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