經過十年，科學家們揭示了蒼蠅大腦的驚人細節

Recently The New York Times reported the following:

After a Decade, Scientists Unveil Fly Brain in Stunning Detail

Scientists have mapped out how 140,000 neurons are wired in the brain of the fruit fly, Drosophila melanogaster.

By Carl Zimmer - The New York Times Science Section

Oct. 2, 2024

A fruit fly’s brain is smaller than a poppy seed, but it packs tremendous complexity into that tiny space. Over 140,000 neurons are joined together by more than 490 feet of wiring, as long as four blue whales placed end to end.

Hundreds of scientists mapped out those connections in stunning detail in a series of papers published on Wednesday in the journal Nature. The wiring diagram will be a boon to researchers who have studied the nervous system of the fly species, Drosophila melanogaster, for generations.

Previously, a tiny worm was the only adult animal to have had its brain entirely reconstructed, with just 385 neurons in its entire nervous system. The new fly map is “the first time we’ve had a complete map of any complex brain,” said Mala Murthy, a neurobiologist at Princeton who helped lead the effort.

Other researchers said that analyzing the circuitry in the fly brain would reveal principles that apply to other species, including humans, whose brains have 86 billion neurons.

In one of the new studies, the researchers tackled the mystery of how sensory signals flow through the brain and prompt it to produce commands. They created a computer simulation of the complete fly brain. When presented with simulated tastes, the artificial brain produced signals to stick out the tongue.

Sebastian Seung, another leader of the project at Princeton, said the simulations reminded him of long-running speculations about how “mind uploading” could allow us to transfer our brains into computers.

“Mind uploading has been a science fiction, but now mind uploading — for a fly, at least — is becoming mainstream science,” Dr. Seung said.

The mapping began in 2013, when Davi Bock, a neuroscientist then at the Janelia Research Campus of the Howard Hughes Medical Institute in Virginia, and his colleagues dunked the brain of an adult fly in a chemical bath, hardening it into a solid block. They shaved an exquisitely thin layer off the top of the block and used a microscope to take pictures of it.

Then the scientists shaved another layer and took a new picture. To capture the entire brain, they imaged 7,050 sections and produced about 21 million pictures.

Dr. Seung and his colleagues also developed software to interpret these images. They programmed computers to recognize the cross-sections of neurons in each picture and stack them into the 3-D shapes of the cells.

The computers sometimes made mistakes, such as by creating two neurons that passed straight through each other. A team of Drosophila experts and enthusiasts inspected the map and corrected its errors.

It took more than a decade for the scientists to produce the first high-resolution model of the fly brain. Based on the different shapes of the neurons, Gregory Jefferis, a neuroscientist at the University of Cambridge, and his colleagues classified the cells into 8,453 distinct types, making it the biggest catalog of cell types in any brain. (Scientists have identified only 3,300 cell types in the human brain.)

By tracing the neurons through the map, Dr. Murthy and her colleagues have gleaned clues about what those different types of cells do.

Some types of neurons, for example, command walking flies to come to a halt. One circuit, researchers found, stops the flies by blocking the walking commands, and a second stops a fly by stiffening its leg joints.

Philip Shiu and his colleagues at the University of California, Berkeley, used the map to build a virtual fly brain, with simulated neurons passing signals to connected cells.

Dr. Shiu’s team tested the simulated brain by seeing how it responded to food. A fly’s tongue-like proboscis is covered in neurons that are sensitive to sugar. The researchers activated them and watched the signals race through the fly’s brain.

The simulated brain did what a real brain would: It commanded the proboscis to stick out so that the fly could eat. And if the virtual fly tasted sugar only on the right side of its proboscis, the brain sent commands to bend it toward the right.

Anita Devineni, a Drosophila expert at Emory University who was not involved in the project, said she relied on the new resource to plan new experiments. “We’re using this for everything we do,” she said.

Dr. Murthy and her colleagues hope to use the fly map to discover fundamental rules for complex brains, such as how the wiring of neurons allows signals to spread across an entire brain quickly. But they also recognize that bigger brains may not follow all of the same rules.

Now researchers are embarking on a far more ambitious map: a mouse brain, which contains about 1,000 times as many neurons as a fly.

Hongkui Zeng, a neuroscientist at the Allen Institute for Brain Science in Seattle who was not involved in the project, said that the completion of the fly map could help speed up the mouse brain project. Dr. Zeng said such improvements were essential to complete the new map in our lifetimes.

“Any improvement could make a large difference,” Dr. Zeng said. “We can’t wait 10,000 years.”

Translation

經過十年，科學家們揭示了蒼蠅大腦的驚人細節

科學家已經繪製出果蠅 (Drosophila melanogaster) 大腦中 14 萬個神經元的連結方式。

果蠅的大腦比罌粟籽還小，但它卻在這個狹小的空間裡蘊藏著巨大的複雜性。只要四頭藍鯨首尾相連，即透過超過490 英尺的長度, 就把超過 14 萬個神經元連接在一起。

週三在《自然》雜誌上發表的一系列論文中，數百名科學家以驚人的細節描繪了這些連結。這張接線圖對於幾代研究果蠅 (Drosophila melanogaster) 神經系統的研究人員來說將是一個大幫助。

在這之前，微小的蠕蟲是唯一一種大腦完全被重組出來的成年動物，整個神經系統只有 385 個神經元。幫助領導今次工作的普林斯頓大學神經生物學家Mala Murthy 表示，新的果蠅圖是「我們第一次擁有任何複雜大腦的完整繪圖」。

其他研究人員表示，分析果蠅大腦中的電路將揭示適用於其他物種的原理，包括人類，人類的大腦有 860 億個神經元。

在一項新研究中，研究人員解開了感覺訊號如何流經大腦並促使其產生命令的謎團。他們創建了完整的果蠅大腦的電腦模擬。當有模擬的味道時出現，人造大腦會產生伸出舌頭的訊號。

普林斯頓大學該計畫的另一位負責人 Sebastian Seung 表示，這些模擬讓他想起了長期以來猜測關於「思維上傳」如何讓我們將大腦轉移到電腦。

Seung 博士說: 「思維上傳一直是科幻小說，但現在思維上傳 - 至少對於蒼蠅來說 - 正在成為主流科學」。

繪圖始於2013 年，當時維吉尼亞州霍華休斯醫學研究所Janelia Research Campus的神經科學家Davi Bock和他的同事將一隻成年蒼蠅的大腦進行化學浴，使其硬化成固體塊。他們從固體的頂部刮掉出一片非常薄的上層，並使用顯微鏡對其進行了拍照。

然後科學家們又剃掉了一層並拍攝了一張新照片。為了捕捉整個大腦，他們對 7,050 個截面斷片進行拍照，並產生了約 2,100 萬張圖片。

Seung 博士和他的同事也開發了軟體來解釋這些圖像。他們對電腦進行編程，以識別每張圖片中神經元的橫截面，並將它們堆疊成細胞的 3D 形狀。

電腦有時會犯錯誤，例如把直接穿過彼此的一神經元當作成為兩個。由果蠅專家和愛好者組成的團隊檢查繪圖並糾正了錯誤。

科學家花了十多年的時間才製作了第一個果蠅大腦的高解析度模型。劍橋大學的神經科學家 Gregory Jefferis 和他的同事根據神經元的不同形狀，將細胞分為 8,453 種不同類型，使其成為任何大腦中最大的細胞類型目錄。 （科學家僅鑑定出人類大腦中的 3,300 種細胞類型。）

透過在繪圖上追蹤神經元，Murthy博士和她的同事們收集這些不同類型細胞的作用的有關線索。

例如某些類型的神經元會命令行走的蒼蠅停下來。研究人員發現，一條神經線路用於發出命令阻止蒼蠅歩行，另一個神經線路用於僵硬化腿部關節來停止蒼蠅。

加州大學柏克萊分校的 Philip Shiu 和他的同事使用該繪圖建構了一個虛擬的蒼蠅大腦，其中模擬神經元將訊號傳遞給連接的細胞。

Shiu博士的團隊透過觀察模擬大腦對食物的反應來做測試。蒼蠅像舌頭一樣的長嘴覆蓋著對糖敏感的神經元。研究人員激活它們並觀察信號在果蠅大腦中的快速傳輸。

模擬大腦的行為與真實大腦的行為相同：它命令長嘴伸出，以便蒼蠅可以進食。如果虛擬蒼蠅只在其長嘴右側嚐到了糖的味道，大腦就會發出命令將其向右彎曲。

Emory大學的果蠅專家Anita Devineni沒有參與該項目，她說她依靠新資料來規劃新的實驗。 她說“我們所做的一切都使用它”。

Murthy博士和她的同事希望利用果蠅圖來發現複雜大腦的基本規則，例如神經元的連接如何使訊號快速傳播到整個大腦。但他們也認識到，更大的大腦可能不會完全遵循相同的規則。

現在，研究人員正在著手繪製一幅更有野心的圖像：小鼠大腦，其神經元數量大約是蒼蠅的 1000 倍。

沒有參與這項研究該計劃的西雅圖艾倫腦科學研究所的神經科學家Hongkui Zeng博士表示，果蠅圖的完成有助於加快小鼠大腦計畫的進度。Zeng博士表示，這些改進對於我們有生之年完成新圖至關重要。

Zeng 博士說: 「任何改進都可能產生很大的變化」; 「我們等不了一萬年」。

              So, in a new study researchers have created a computer simulation of a complete fly’s brain. Based on the different shapes of the neurons in this brain, a neuroscientist has classified the cells into 8,453 distinct types. I think the creation of this computer simulation of the brain is an important step for scientists to unveil the secrets of the human brain.