跟著城市嚮導「老臺北胃」，用味道認識臺北

很多朋友來臺北，
都會問我同一個問題：
「臺北小吃那麼多，到底該從哪裡開始吃？」
夜市裡攤位一字排開、老店藏在巷弄轉角，
看起來都很有名，卻又怕吃錯、踩雷，
結果行程走完，反而沒真正記住臺北的味道。
我常被朋友笑說是「老臺北胃」。
不是因為特別會吃，而是因為在這座城市待久了，
知道哪些味道是陪著臺北人成長的日常。
這篇文章，就是我整理的一份清單。
如果你第一次來臺北，
我會帶你從這 10 樣最具代表性的臺北小吃開始，
不追一時爆紅、不走浮誇路線，
而是讓你吃完後能真正理解
原來，這就是臺灣的小吃文化。
跟著老臺北胃走，
用最簡單的方式，
把臺北的味道，一樣一樣記在心裡。

我怎麼選出這 10 大臺北小吃？

在臺北，
你隨便走進一條夜市或老街，
都可以輕易列出 30 種以上的小吃。
所以這份清單，
不是「臺北最好吃」的排名，
 而是我站在「第一次來臺北的旅客」角度，
做的推薦。
身為一個被朋友稱作「老臺北胃」的人，
我選這 10 樣小吃時，心裡一直放著幾個原則。

一吃就知道：這就是臺灣味

燒烤、火鍋很好吃，
但換個城市、換個國家，也吃得到。
我挑的，是那種
只要一入口，就會讓人聯想到的臺灣味。
 不需要解釋太多，舌頭就能懂。

不只是好吃，而是有「臺北日常感」

臺北的小吃迷人，
不只在味道，
而在它融入生活的方式。
我在意的是：

1. 會不會出現在早餐、宵夜、下班後
2. 有沒有陪伴這座城市很久的記憶

吃完之後，你會記得臺北

最後一個標準很簡單。
如果你回到家，
還會突然想起某個味道、某碗熱湯、某個攤位的香氣
那它就值得被放進這份清單裡。

接下來的 10 樣臺北小吃，
就是我會親自帶朋友去吃的在地美食。
不趕行程、不拚數量，
而是一口一口，
慢慢認識臺北。

第 1 家：饌堂－黑金滷肉飯（雙連店）｜一碗就懂臺灣人的日常

如果只能用一道料理，
 來解釋臺灣人的日常飲食，
 那我一定會先帶你吃滷肉飯。
在臺北，滷肉飯不是什麼特別的節慶料理，
 而是從早餐、午餐到宵夜，
 默默陪著很多人長大的味道。
而在眾多滷肉飯之中，
饌堂－黑金滷肉飯（雙連店），
 我很常帶第一次來臺北的朋友造訪的一家。

為什麼第一站，我會選饌堂？
饌堂的滷肉飯，走的是**「黑金系」路線**。
滷汁顏色深、香氣厚，
卻不死鹹、不油膩。
滷肉切得細緻，
肥肉入口即化，搭配熱騰騰的白飯，
每一口都是很完整、很臺灣的味道。
對第一次吃滷肉飯的旅客來說，
這種風味夠經典、也夠穩定，
不需要太多心理準備，就能理解為什麼臺灣人這麼愛它。

不只是好吃，而是「現在的臺北感」
饌堂並不是那種躲在深巷裡的老攤，
空間乾淨、節奏俐落，
卻沒有失去滷肉飯該有的靈魂。
這也是我會推薦給旅客的原因之一：
它保留了臺灣小吃的核心味道，
同時也讓第一次來臺北的人，
吃得安心、坐得舒服。

老臺北胃的帶路小提醒
如果是第一次來：

1. 一定要點招牌黑金滷肉飯
   
2. 可以加一顆滷蛋，風味會更完整
3. 搭配簡單的小菜，就很有臺灣家常感

這不是那種吃完會驚呼「哇！」的料理，
而是會讓你在幾口之後，
慢慢理解
原來，臺灣人的日常，就是這樣被一碗飯照顧著。

地址：103臺北市大同區雙連街55號1樓

電話：0225501379

菜單：https://bio.site/ZhuanTang

第 2 家：富宏牛肉麵｜臺北深夜也醒著的一碗熱湯

如果說滷肉飯代表的是臺灣人的日常，
 那牛肉麵，
 就是很多臺北人心中最有份量的一餐。
而在臺北提到牛肉麵，
 富宏牛肉麵，
 幾乎是夜貓族、加班族、外地旅客一定會被帶去的一站。

為什麼老臺北胃會帶你來吃富宏？
富宏最讓人印象深刻的，
不是華麗裝潢，
而是那鍋永遠冒著熱氣的紅燒湯頭。
湯色濃而不混，
帶著牛骨與醬香慢慢熬出的厚度，
喝起來溫潤、不刺激，
卻會在嘴裡留下很深的記憶點。
牛肉給得大方，
燉到軟嫩卻不鬆散，
搭配彈性十足的麵條，
每一口都很直接、很臺北。

不分時間，任何時候都適合的一碗麵
富宏牛肉麵最迷人的地方，
在於它陪伴了無數個臺北的夜晚。
不管是深夜下班、看完演唱會、
或是剛抵達臺北、還沒適應時差，
這裡總有一碗熱湯在等你。
對旅客來說，
這種不用算時間、不用擔心打烊的安心感，
本身就是一種臺北特色。

老臺北胃的帶路小提醒
第一次來富宏，我會這樣點：

1. 紅燒牛肉麵是首選
   
2. 如果想吃得更過癮，可以加點牛筋或牛肚
3. 湯先喝一口原味，再視情況調整辣度

這不是精緻料理，
卻是一碗能在任何時刻撐住你的牛肉麵。
在臺北，
很多夜晚，
就是靠這樣一碗熱湯走過來的。

地址：108臺北市萬華區洛陽街67號

電話：0223713028

菜單：https://www.facebook.com/pages/富宏牛肉麵-原建宏牛肉麵/

第 3 家：士林夜市・吉彖皮蛋涼麵｜臺北夏天最有記憶點的一口清爽

如果你在夏天來到臺北，
 一定會很快發現一件事
 這座城市，真的很熱。
也正因為這樣，
 臺北的小吃世界裡，
 才會出現像「涼麵」這樣的存在。
而在士林夜市，
 吉彖皮蛋涼麵，
 就是我很常帶旅客來吃的一家。

為什麼在夜市，我會帶你吃涼麵？
很多人對夜市的印象，
都是炸物、熱湯、重口味。
但真正的臺北夜市，
其實也很懂得照顧人的胃。
吉彖的涼麵，
冰涼的麵條拌上濃郁芝麻醬，
再加上切得細緻的皮蛋，
入口的第一瞬間，
就是一種「被降溫」的感覺。
那種清爽，
不是沒味道，
而是在濃香與清涼之間取得剛剛好的平衡。

皮蛋，是靈魂，也是臺灣味的關鍵
對很多外國旅客來說，
皮蛋是既好奇、又有點猶豫的存在。
但我常說，
如果要嘗試皮蛋，
涼麵是一個非常溫柔的起點。
芝麻醬的香氣會先接住味蕾，
皮蛋的風味則在後段慢慢出現，
不衝、不嗆，
反而多了一層深度。
很多人吃完後，
都會露出那種「原來是這樣啊」的表情。

老臺北胃的帶路小提醒
第一次點吉彖皮蛋涼麵，我會建議：

1. 一定要選皮蛋款，才吃得到特色
2. 醬料先拌勻，再吃，風味會更完整
3. 如果天氣真的很熱，這一碗會救你一整晚

這不是華麗的小吃，
卻非常臺北。
在悶熱的夜晚，
站在夜市人潮裡，
吃著一碗涼麵，
你會突然明白——

原來臺北的小吃，連氣候都一起考慮進去了。

地址：111臺北市士林區基河路114號

電話：0981014155

菜單：https://www.facebook.com/profile.php?id=100064238763064

第 4 家：胖老闆誠意肉粥｜臺北人深夜最踏實的一碗粥

如果你問我，
 臺北人在深夜、下班後，
 最容易感到被安慰的食物是什麼——
 我會毫不猶豫地說：肉粥。
而提到肉粥，
 胖老闆誠意肉粥，
 就是很多老臺北人口中的那一味。

為什麼這一碗粥，會被叫做「誠意」？
胖老闆的肉粥，看起來很簡單。
白粥、肉燥、配菜，
沒有華麗擺盤，也沒有複雜作法。
但真正坐下來吃，你會發現：
這碗粥，不敷衍任何一個細節。
粥體滑順、不稀薄，
肉燥香而不膩，
搭配各式家常小菜，
一口一口吃下去，
很自然就會放慢速度。
這種味道，
不是要你驚艷，
而是要你安心。

這不是觀光小吃，而是臺北人的生活片段
胖老闆誠意肉粥，
最迷人的地方，
就是它的客人。
你會看到：

1. 剛下班的上班族
2. 熬夜後來吃一碗熱粥的人
3. 熟門熟路、點菜不用看菜單的老客人

這些畫面，
比任何裝潢都更能說明這家店在臺北的位置。
對旅客來說，
這是一個走進臺北人日常的入口。

老臺北胃的帶路小提醒
第一次來吃，我會這樣建議：

1. 肉粥一定要點，這是主角
2. 配幾樣小菜一起吃，才有完整體驗
3. 不用急，慢慢吃，這碗粥就是要你放鬆

這不是為了拍照而存在的小吃，
而是那種
**會讓人記得「那天晚上，我在臺北吃了一碗很溫暖的粥」**的味道。

地址：10491臺北市中山區長春路89-3號

電話：0913806139

菜單：https://lin.ee/xxbYZyS

第 5 家：圓環邊蚵仔煎｜夜市裡最不能缺席的臺灣經典

如果要選一道
 最常出現在旅客記憶裡的臺灣小吃，
 蚵仔煎一定排得上前幾名。
而在臺北，
 圓環邊蚵仔煎，
 就是那種很多臺北人從小吃到大的存在。

為什麼蚵仔煎，這麼能代表臺灣？
蚵仔煎的魅力，
不在於精緻，
而在於它把幾種看似簡單的食材，
煎成了一種獨特的口感。
新鮮蚵仔的海味、
雞蛋的香氣、
地瓜粉形成的滑嫩外皮，
最後再淋上甜中帶鹹的醬汁，
一口下去，
就是夜市的完整畫面。
這種味道，
很難在其他國家找到替代品。

圓環邊，吃的是記憶感
圓環邊蚵仔煎，
沒有多餘的包裝，
也不刻意迎合潮流。
它留下來的原因很簡單
味道夠穩、節奏夠快、
讓人一吃就知道「對，就是這個」。
對旅客來說，
這是一家
不需要研究、不需要比較，就能安心點蚵仔煎的地方。

老臺北胃的帶路小提醒
第一次吃蚵仔煎，我會這樣建議：

1. 趁熱吃，口感最好
   
2. 不用急著加辣，先吃原味
3. 醬汁是靈魂，別急著把它拌掉

蚵仔煎不是細嚼慢嚥的料理，
它屬於人聲鼎沸、鍋鏟作響的夜市時刻。
站在人群裡，
吃著一盤熱騰騰的蚵仔煎，
你會很清楚地感受到
這，就是臺北的夜晚。

地址：103臺北市大同區寧夏路46號

電話：0225580198

菜單：https://oystera.com.tw/menu

第 6 家：阿淑清蒸肉圓｜第一次吃肉圓，就該從這裡開始

說到臺灣小吃，
 很多人腦中一定會出現「肉圓」兩個字。
但真正吃過之後才會發現，
 肉圓，從來不只有一種樣子。
在臺北，
 阿淑清蒸肉圓，
 就是我很常拿來介紹「清蒸派肉圓」的一家。

清蒸肉圓，和你想像的不一樣
不少旅客對肉圓的第一印象，
來自油炸版本，
外皮厚、口感重。
而阿淑的清蒸肉圓，
完全是另一個方向。
外皮晶瑩、滑嫩，
帶著自然的彈性，
不油、不膩，
一入口反而顯得清爽。
內餡扎實，
豬肉香氣清楚，
搭配特製醬汁，
味道層次簡單卻很乾淨。

為什麼我會推薦給第一次來臺北的旅客？
因為這顆肉圓，
不需要適應期。
它不刺激、不厚重，
即使是第一次嘗試臺灣小吃的人，
也能輕鬆接受。
對旅客來說，
這是一顆
「吃得懂、也記得住」的肉圓。

老臺北胃的帶路小提醒
第一次來阿淑，我會這樣吃：

1. 直接點一顆清蒸肉圓，吃原味
2. 醬汁先別全部拌開，邊吃邊調整
3. 放慢速度，感受外皮的口感變化

這不是夜市裡熱鬧喧囂的料理，
而是那種
安靜地展現臺灣小吃功夫的味道。
當你吃完這顆肉圓，
會更明白一件事
臺灣小吃的魅力，
往往藏在這些細節裡。

地址：242新北市新莊區復興路一段141號

電話：0229975505

第 7 家：胡記米粉湯｜一碗最貼近臺北早晨的味道

如果說前面幾樣小吃，
 是臺北的熱鬧與記憶，
 那麼米粉湯，
 就是這座城市最真實的日常。
而在臺北，
 胡記米粉湯，
 是很多人從小吃到大的存在。

為什麼米粉湯，這麼「臺北」？
米粉湯不是重口味料理，
它靠的不是刺激，
而是一碗清澈卻有深度的湯。
胡記的湯頭，
用豬骨慢慢熬出香氣，
喝起來清爽、不油，
卻能在喉嚨留下溫度。
米粉細軟，
吸附湯汁後入口順滑，
簡單到不能再簡單，
卻正是臺北人習以為常的早晨風景。

配菜，才是這一碗的靈魂延伸
在胡記吃米粉湯，
主角雖然是湯，
但真正讓人滿足的，
往往是那些小菜。
紅燒肉、豬內臟、燙青菜，
隨意點上幾樣，
湯一口、菜一口，
就是很多臺北人記憶中的早餐組合。
對旅客來說，
這是一種
不需要解釋，就能融入的臺北生活感。

老臺北胃的帶路小提醒
第一次來胡記，我會這樣建議：

1. 一定要點米粉湯，湯先喝
2. 再配 1～2 樣小菜，體驗會完整很多
3. 這一餐適合慢慢吃，不用趕

這不是為了觀光而存在的小吃，
而是一碗
每天準時出現在臺北人生活裡的湯。
當你坐在店裡，
聽著湯勺碰撞的聲音，
你會突然感覺到——
原來，臺北的早晨，
就是從這樣一碗米粉湯開始的。

地址：106臺北市大安區大安路一段9號1樓

電話：0227212120

第 8 家：藍家割包｜一口咬下的臺灣街頭記憶

如果要選一道
 外國旅客一看到就會好奇、吃完又會記住的小吃，
 割包，一定在名單裡。
而在臺北，
 藍家割包，
 就是我很放心帶旅客來認識這道經典的一站。

割包，為什麼被叫做「臺灣漢堡」？
割包的結構其實很簡單：
鬆軟的白饅頭、
燉得入味的滷五花肉、
酸菜、花生粉、香菜。
但真正迷人的，
是這些元素組合在一起時，
形成的層次感。
肉香、甜味、鹹味、清爽度，
在一口之間同時出現，
沒有誰搶戲，
卻彼此剛好。
這種平衡感，
正是臺灣小吃很迷人的地方。

藍家割包不是走浮誇路線，
它給人的感覺很直接
就是你期待中的割包樣子。
饅頭柔軟不乾，
五花肉肥瘦比例恰到好處，
入口即化卻不膩口，
花生粉的甜香收尾，
讓整體味道非常完整。
對第一次吃割包的旅客來說，
這是一個
不會出錯、也很容易愛上的版本。

老臺北胃的帶路小提醒
第一次吃藍家割包，我會這樣建議：

1. 直接點招牌割包，不要改配料
2. 如果有香菜，建議保留，味道會更完整
3. 趁熱吃，饅頭口感最好

割包不是精緻料理，
卻非常有記憶點。
站在街頭，
拿著一顆熱騰騰的割包，
邊走邊吃，
你會很清楚地感受到
這一口，就是臺灣的街頭生活。

地址：100臺北市中正區羅斯福路三段316巷8弄3號

電話：0223682060

菜單：https://instagram.com/lan_jia_gua_bao?utm_medium=copy_link

第 9 家：御品元冰火湯圓｜臺北夜晚最溫柔的一碗甜

吃了一整天的臺北小吃，
 到了這個時候，
 胃其實已經差不多滿了。
但只要天氣一涼，
 或夜色慢慢降下來，
 你還是會想找一碗——
 不是為了吃飽，而是為了舒服的甜點。
這時候，我通常會帶你來 御品元冰火湯圓。

為什麼叫「冰火」？這碗湯圓的關鍵就在這裡
御品元最有特色的地方，
就在於它的「冰火交錯」。
熱騰騰的湯圓，
外皮軟糯、內餡濃香，
搭配冰涼清甜的桂花蜜湯，
一口下去，
溫度在嘴裡交替出現。
不是衝突，
而是一種很細膩的平衡。
這樣的吃法，
也正是臺灣甜點很擅長的地方——
不張揚，但很有記憶點。

這是一碗，會讓人慢下來的甜點
和夜市裡熱鬧的甜品不同，
御品元的冰火湯圓，
更像是一個讓人停下腳步的存在。
你會發現，
坐在這裡吃湯圓的人，
說話聲都會不自覺地變小。
對旅客來說，
這不只是吃甜點，
而是一個
把白天的熱鬧慢慢收進回憶裡的時刻。

老臺北胃的帶路小提醒
第一次吃御品元，我會這樣建議：

1. 點招牌冰火湯圓，體驗完整特色
2. 先單吃湯圓，再搭配湯一起吃
3. 放慢速度，這一碗不適合趕時間

這不是為了拍照而存在的甜點，
而是一碗
會讓你記得「那天晚上在臺北，很舒服」的湯圓。

地址：106臺北市大安區通化街39巷50弄31號

電話：0955861816

菜單：https://instagram.com/lan_jia_gua_bao

第 10 家：頃刻間綠豆沙牛奶專賣店｜把臺北的味道，留在最後一口清甜

走到這一站，
 其實已經不需要再吃什麼大份量的東西了。
這時候，
 最適合的，
 是一杯不吵鬧、不張揚，
 卻會默默留在記憶裡的飲品。
頃刻間綠豆沙牛奶，
 就是我很常用來替一天畫下句點的選擇。

綠豆沙牛奶，為什麼這麼「臺灣」？
在臺灣，
飲料不只是解渴，
而是一種生活節奏。
綠豆沙牛奶看起來簡單，
但真正好喝的版本，
靠的是火候、比例，
還有耐心。
頃刻間的綠豆沙，
口感細緻、不粗顆，
甜度自然、不膩口，
牛奶的加入，
讓整杯變得柔順而溫和。
這不是衝擊味蕾的飲料，
而是一種
喝完之後，會覺得剛剛那一刻很舒服的甜。

為什麼我會用它當作最後一站？
因為它很臺北。
你可以外帶，
邊走邊喝；
也可以站在店門口，
慢慢把杯子喝空。
沒有儀式感，
卻很真實。
對旅客來說，
這杯綠豆沙牛奶，
就像是把今天吃過的所有味道，
溫柔地整理好，
帶走。

老臺北胃的帶路小提醒
第一次喝頃刻間，我會這樣建議：

1. 直接點招牌綠豆沙牛奶
   
2. 正常甜就很剛好，不用特別調整
3. 找個角落慢慢喝，別急著趕路

這一杯，
不會讓你驚呼，
卻會在回程的路上，
突然想起來。
原來，臺北的味道，是這樣結束一天的。

地址：111臺北市士林區小北街1號

電話：0228818619

菜單：https://instagram.com/chill_out_moment?igshid=YmMyMTA2M2Y=

如果只有 3 天的自助旅行在臺北，怎麼吃這 10 家？

第一次來臺北，
時間有限、胃容量也有限，
與其每一家都趕，不如照著節奏吃。
這份 3 天小吃路線，
是老臺北胃會帶朋友實際走的版本：
不爆走、不硬塞，
讓你每天都吃得剛剛好。

臺北 3 天小吃推薦行程表（老臺北胃版本）

天數	時段	店家名稱	小吃類型
Day 1	午餐	饌堂－黑金滷肉飯（雙連店）	滷肉飯
Day 1	下午	阿淑清蒸肉圓	肉圓
Day 1	晚餐	富宏牛肉麵	牛肉麵
Day 1	宵夜	胖老闆誠意肉粥	粥品
Day 2	早餐	胡記米粉湯	米粉湯
Day 2	下午	藍家割包	割包
Day 2	晚上	士林夜市－吉彖皮蛋涼麵	涼麵
Day 2	夜市	圓環邊蚵仔煎	蚵仔煎
Day 3	下午	御品元冰火湯圓	甜點
Day 3	收尾	頃刻間綠豆沙牛奶專賣店	飲品

雖然每個小吃的地點都有一點距離，但是你也知道，好吃的小吃，是值得你花一點時間前往品嘗
老臺北胃的小提醒

1. 不需要每一家都點到最滿
2. 留一點餘裕，才會想再回來
3. 臺北小吃的魅力，不在於吃多少，而在於記住了什麼味道
   

當你照著這 3 天走完，
你會發現，
臺北不是靠一兩道名菜被記住的，
而是靠這些看似日常、卻很真實的小吃。
下次再來，老臺北胃再帶你吃更深的那一輪。

老臺北胃帶路｜這 10 口，就是我心中的臺北

寫到這裡，
 其實已經不是在推薦哪一家小吃了。
而是在回頭看，
 這座城市，是怎麼用食物陪著人生活的。
滷肉飯、牛肉麵、肉粥、米粉湯，
 不是為了成為觀光名單而存在，
 而是每天默默出現在臺北人的日子裡。
夜市裡的蚵仔煎、涼麵、割包，
 熱鬧、吵雜、節奏很快，
 卻也正是臺北最真實的樣子。
而最後那碗湯圓、那杯綠豆沙牛奶，
 則是在一天結束時，
 替味蕾留下一個溫柔的句點。

如果你問我，
「這 10 家是不是臺北最好吃的小吃？」
我會說，
它們不一定是排行榜第一名，
卻是我真的會帶朋友去吃的版本。
因為它們吃得到：

1. 臺北人的日常
2. 巷弄裡的熟悉感
3. 不需要解釋，就能被理解的味道

如果你是第一次來臺北，
跟著這份清單走，
你不一定會吃得最飽，
但你一定會記得——
臺北，是什麼味道。
而如果有一天，
你又再回到這座城市，
走進熟悉的街口、
看到冒著熱氣的小攤，
你也會開始懂得，
為什麼老臺北胃，
總是記得這些看似平凡的滋味。
因為，真正留在心裡的，
從來不是吃過多少，
而是哪一口，讓你想起臺北。

圓環邊蚵仔煎當點心適合嗎？

走完這 10 家，

你可能會發現一件事胖老闆誠意肉粥在地人怎麼說？

臺北的小吃，其實不急著被你記住。

它們就安靜地存在在街角、夜市、轉彎處，頃刻間綠豆沙牛奶專賣店推薦點什麼？

等你有一天，再回到這座城市。藍家割包口味會太清淡嗎？

如果你是第一次來臺北，胡記米粉湯一定要點嗎？

希望這份「老臺北胃帶路」的清單，

能幫你少一點猶豫、多一點安心。

不用擔心踩雷，阿淑清蒸肉圓一定要點嗎？

也不用為了排行而奔波，藍家割包會不會太油？

只要照著節奏走，

你就會吃到屬於自己的臺北味道。

而如果你已經來過臺北，

那更希望這篇文章，阿淑清蒸肉圓吃起來順口嗎？

能帶你走進那些

你可能錯過、卻一直都在的日常小吃。

因為真正迷人的旅行，

從來不是把清單全部打勾，

而是某一天，

你突然想起那碗飯、那口湯、那杯甜，胡記米粉湯長輩會喜歡嗎？

然後在心裡對自己說一句：饌堂－黑金滷肉飯（雙連店）冬天適合吃嗎？

「下次再去臺北，還想再吃一次。」

把這篇文章存起來、分享給一起旅行的人，

或是在規劃行程時，再回來看看。

讓味道，成為你認識臺北的方式。

下一次來臺北，

別急著走遠。

老臺北胃，御品元冰火湯圓觀光客推薦嗎？

會一直在這些地方，

等你再回來。

A combination of microscopy, tissue preparation, and data innovations could yield first-of-their-kind brain atlases that specify the locations and types of all of the brain’s 180+ billion cells. Credit: Hillman Lab/Columbia’s Zuckerman Institute Columbia-led team wins $9.1 million research grant to create fundamentally new maps that will chart cell diversity throughout the brains of humans. Researchers at Columbia University and the Icahn School of Medicine are collaborating on a project to create atlases of entire human brains, including all 180 billion cells and counting. This kind of data can help uncover how the structure and organization of the brain give rise to behavior, emotion, and cognition, in sickness and in health. Until now, cellular-level brain atlasing has been limited to much smaller animals or just smaller sections of the human brain due to the enormous amount of time and vast technical complexity needed for mapping the whole human brain. The Power of New Technology: HOLiS Microscopy “Throughout the history of science, new tools have been behind some of the most dramatic advances,” said Elizabeth Hillman, PhD, a Herbert and Florence Irving Professor at Columbia’s Zuckerman Institute and leader of the project. “We are developing technologies that should make high-speed, large-scale imaging of tens or even hundreds of human brains a feasible prospect in the next five years. The unprecedented troves of data that we hope to produce should open the way to previously inaccessible knowledge about the human brain.” To enable Dr. Hillman and her collaborators to undertake this ambitious project, the National Institutes of Health BRAIN Initiative recently awarded them a $9.1 million grant. The funding will be shared between Columbia University, the Icahn School of Medicine at Mount Sinai and Carnegie Mellon University. Since 2014, the BRAIN Initiative has invested over $2.4 billion in research funding to boost our understanding of how the brain works. The new project falls under the auspices of the BRAIN Initiative Cell Census Network, which was established in 2017 to encourage researchers to find ways to generate comprehensive brain-cell atlases. “If successful, our microscope should be able to image an entire human brain with cellular detail in a matter of days,” said Dr. Hillman, who is also a professor of biomedical engineering and radiology at Columbia. “This data will be like Google Earth for the brain, enabling analysis of patterns and distributions of different types of human brain cells across vastly different length scales. To get a feel for the challenge, keep in mind that there are only eight billion people on earth but over 180 billion cells in the brain.” The team isn’t interested in just counting cells. Developing a brain map charting the diversity of the many different kinds of cells that make up the brain is a top priority. “We know that the brain contains billions of neurons, but there are many different subtypes of neurons,” explains Dr. Hillman. “How many there are, how they are organized, and how they vary between different brain regions and different people is largely unknown.” But the brain isn’t made only of neurons. Its meshwork includes other types of cells, among them a range of glial cells and cells making up the brain’s vasculature. All of these cell types are essential for normal brain function and could hold important clues about what goes wrong in disease. “To make these datasets really useful, we have to find a way to capture as much information as possible as we scan the whole brain,” said Dr. Hillman, who has a track record of inventing new, powerful, and fast microscope techniques. “If successful, our microscope should be able to image an entire human brain with cellular detail in a matter of days.” Innovative Microscopy Techniques for Brain Imaging For this brain-atlasing project, she is developing another new microscope technique. It’s called Human Brain Optimized Light Sheet (HOLiS) microscopy. The team chose the name to emphasize the importance of holistic imaging and analysis of the entire human brain of each individual. The first step in the imaging process is to carefully cut the brain into 5-millimeter-thick sections and process them to make them completely transparent. This almost magical feat is the specialty of co-Principal Investigator on the project, Zhuhao Wu, PhD, assistant professor at Mount Sinai’s Laboratory of Neural Systems, Structures and Genetics. Dr. Wu has optimized a method for the human brain clearing, which includes a step that can infuse each brain section with a range of fluorescent tags that make it possible to identify individual cells and their diverse properties based on their different colors. Then comes the HOLiS microscope, which operates at lightning speed to generate massive, technicolor 3D images of each section. The technique works by projecting laser light into the tissue to create a sheet of light that illuminates a very thin tilted plane, while a fast camera captures an image of the same plane. By moving the brain section at a constant speed, successive images of each plane can be stacked together to form a long 3D block. The tissue is then scanned back and forth to cover its whole volume before moving onto the next section. “Attempting to image a whole human brain with existing conventional instruments would take years,” said Hillman. “We hope our HOLiS system will be able to image an entire brain in about a week.” This kind of speed, added Hillman, will take whole-brain imaging from a one-off proof of concept to a technology capable of imaging hundreds of brains. “We suspect that every brain will be very different, so we need to be able to image a lot of brains to understand brain diversity across the lifespan, and to ultimately be able to explore a wide range of diseases and disorders.” Managing and Analyzing Massive Brain Data Another challenge remains, however. The team expects each brain-atlasing run to generate some two petabytes of data, a massive amount. Collaborators at the Pittsburgh Supercomputing Center at Carnegie Mellon will help the team to convert these torrents of data into more manageable, searchable, and user-friendly databases that can be analyzed and compared. Contributing to this crucial aspect of the project with expertise in computer science, machine vision, information theory, and statistics are Carl Vondrick, PhD, and Cynthia Rush, PhD, from Columbia’s Data Science Institute as well as Luke Hammond, Director of the Zuckerman Institute’s Cellular Imaging Core. Among others joining in the effort are Dr. Wu’s colleagues at the Icahn School of Medicine, including John F. Crary, MD, PhD, director of the school’s Neuropathology Brain Bank and an expert in human brain preservation and neuropathology. Alan Seifert, PhD, assistant professor at Mount Sinai’s Biomedical Engineering and Imaging Institute, will acquire detailed magnetic resonance images of the whole brain before it is cut. This will enable all of the data collected with HOLiS to be registered to current brain atlases and analyzed to compare cellular-level HOLIS data to MRI signal properties. The Icahn team also includes Bradley Delman, MD, professor of radiology, and Patrick Hof, MD, professor of neuroscience, who will contribute their special expertise in neuroradiology and neuroanatomical reading of human brain data. Adding to the mix of talent on the project is Pavel Osten, MD, PhD, a pioneer in the field of whole-brain cellular imaging and now president, founder, and Chief Scientific Officer of a new start-up company. Dr. Osten was instrumental in planning the project and will provide guidance and advice on the best ways to rapidly analyze HOLiS images to find all of the cells and to map information from HOLiS scans onto established anatomical atlases of the human brain. “If we can streamline the process we can build a foundational database that enables analysis of the human brain like never before,” said Dr. Hillman. “Having this data should accelerate our efforts to understand what so often goes right in the human brain and what goes wrong in developmental, neurological, and psychiatric disorders. Award details are as follows: “Cell type atlasing of whole human brains using HOLiS: an optimized pipeline for staining, clearing, imaging, and analysis” (1RF1MH128969-01) Total Award: $9,121,879 over three years.

New research reveals that a long-overlooked genetic anomaly in birds has significantly altered our understanding of their evolutionary lineage, demonstrating that the avian family tree is more complex than previously believed, with implications for the evolutionary analysis of other organisms. An enormous meteor spelled doom for most dinosaurs 65 million years ago. But not all. In the aftermath of the extinction event, birds — technically dinosaurs themselves — flourished. Scientists have spent centuries trying to organize and sort some 10,000 species of birds into one clear family tree to understand how the last surviving dinosaurs filled the skies. Cheap DNA sequencing should have made this simple, as it has for countless other species. But birds were prepared to deceive us. In a pair of new research papers released today, April 1, scientists reveal that another event 65 million years ago misled them about the true family history of birds. They discovered that a section of one chromosome spent millions of years frozen in time, and it refused to mix together with nearby DNA as it should have. This section, just two percent of the bird genome, convinced scientists that most birds could be grouped into two major categories, with flamingos and doves as evolutionary cousins. The more accurate family tree, which accounts for the misleading section of the genome, identifies four main groups and identifies flamingos and doves as more distantly related. A greater flamingo in Mallorca, Spain. Unraveling a genetic mystery revealed that flamingos and doves are more distantly related than previously thought. Credit: Daniel J. Field Breakthrough in Bird Evolution Research “My lab has been chipping away at this problem of bird evolution for longer than I want to think about,” said Edward Braun, Ph.D., the senior author of the paper published in the Proceedings of the National Academy of Sciences and a professor of biology at the University of Florida. “We had no idea there would be a big chunk of the genome that behaved unusually. We kind of stumbled onto it.” Braun supervised an international team of collaborators led by Siavash Mirarab, a professor of computer engineering at the University of California San Diego, to publish their evidence that this sticky chunk of DNA muddied the true history of bird evolution. Mirarab and Braun also contributed to a companion paper published in Nature that outlines the updated bird family tree, which was led by Josefin Stiller at the University of Copenhagen. Both papers are part of the B10K avian genomics project led by Guojie Zhang of Zhejiang University, Erich Jarvis of Rockefeller University, and Tom Gilbert of the University of Copenhagen. Two mutually exclusive bird family trees. The top family tree lumps flamingos and doves, in blue and teal respectively, closely together, while the bottom family tree does not. The top family tree was built around distortions in bird genomes that date back to the extinction of the dinosaurs. The bottom family tree is likely more accurate, after accounting for these genomic anomalies. Credit: Edward Braun Genetic Anomalies and Evolutionary Insights Ten years ago, Braun and his collaborators pieced together a family tree for the Neoaves, a group that includes the vast majority of bird species. Based on the genomes of 48 species, they split the Neoaves into two big categories: doves and flamingos in one group, all the rest in the other. When repeating a similar analysis this year using 363 species, a different family tree emerged that split up doves and flamingos into two distinct groups. With two mutually exclusive family trees in hand, the scientists went hunting for explanations that could tell them which tree was correct. “When we looked at the individual genes and what tree they supported, all of a sudden it popped out that all the genes that support the older tree, they’re all in one spot. That’s what started the whole thing,” Braun said. Investigating this spot, Braun’s team noticed it was not as mixed together as it should have been over millions of years of sexual reproduction. Like humans, birds combine genes from a father and a mother into the next generation. But birds and humans alike first mix the genes they inherited from their parents when creating sperm and eggs. This process is called recombination, and it maximizes a species’ genetic diversity by making sure no two siblings are quite the same. A wompoo fruit-dove in Queensland, Australia. Unraveling a genetic mystery revealed that flamingos and doves are more distantly related than previously thought. Credit: Daniel J. Field Braun’s team found evidence that one section of one bird chromosome had suppressed this recombination process for a few million years around the time the dinosaurs disappeared. Whether the extinction event and the genomic anomalies are related is unclear. The result was that the flamingos and doves looked similar to one another in this chunk of frozen DNA. But taking into account the full genome, it became clear that the two groups are more distantly related. “What’s surprising is that this period of suppressed recombination could mislead the analysis,” Braun said. “And because it could mislead the analysis, it was actually detectable more than 60 million years in the future. That’s the cool part.” Such a mystery could be lurking in the genomes of other organisms as well. “We discovered this misleading region in birds because we put a lot of energy into sequencing birds’ genomes,” Braun said. “I think there are cases like this out there for other species that are just not known right now.” References: “Complexity of avian evolution revealed by family-level genomes” by Josefin Stiller, Shaohong Feng, Al-Aabid Chowdhury, Iker Rivas-González, David A. Duchêne, Qi Fang, Yuan Deng, Alexey Kozlov, Alexandros Stamatakis, Santiago Claramunt, Jacqueline M. T. Nguyen, Simon Y. W. Ho, Brant C. Faircloth, Julia Haag, Peter Houde, Joel Cracraft, Metin Balaban, Uyen Mai, Guangji Chen, Rongsheng Gao, Chengran Zhou, Yulong Xie, Zijian Huang, Zhen Cao, Zhi Yan, Huw A. Ogilvie, Luay Nakhleh, Bent Lindow, Benoit Morel, Jon Fjeldså, Peter A. Hosner, Rute R. da Fonseca, Bent Petersen, Joseph A. Tobias, Tamás Székely, Jonathan David Kennedy, Andrew Hart Reeve, Andras Liker, Martin Stervander, Agostinho Antunes, Dieter Thomas Tietze, Mads Bertelsen, Fumin Lei, Carsten Rahbek, Gary R. Graves, Mikkel H. Schierup, Tandy Warnow, Edward L. Braun, M. Thomas P. Gilbert, Erich D. Jarvis, Siavash Mirarab and Guojie Zhang, 1 April 2024, Nature. DOI: 10.1038/s41586-024-07323-1 “A region of suppressed recombination misleads neoavian phylogenomics” by Siavash Mirarab, Iker Rivas-González, Shaohong Feng, Josefin Stiller, Qi Fang, Uyen Mai, Glenn Hickey, Guangji Chen, Nadolina Brajuka, Olivier Fedrigo, Giulio Formenti, Jochen B. W. Wolf, Kerstin Howe, Agostinho Antunes, Mikkel H. Schierup, Benedict Paten, Erich D. Jarvis, Guojie Zhang and Edward L. Braun, 1 April 2024, Proceedings of the National Academy of Sciences. DOI: 10.1073/pnas.2319506121 This work was supported in part by the National Science Foundation.

Neurons produce rhythmic patterns of electrical activity or oscillations in the brain, driven primarily by memory, according to a recent study. Contrary to previous beliefs, the research showed that these theta oscillations in the hippocampus were more prevalent when individuals were remembering events than experiencing them, highlighting memory as a key driver in theta activity and offering potential pathways for treating brain damage and cognitive impairments. The findings may establish the groundwork for therapy for cognitive impairment and help improve memory. Neurons create rhythmic electrical activity patterns within the brain. A pressing question in neuroscience is the primary driver of these rhythmic signals, known as oscillations. Researchers from the University of Arizona discovered that merely recalling events could set off these oscillations, even more than experiencing the events themselves. The research, published in the journal Neuron, specifically focused on theta oscillations. These occur in the brain’s hippocampus during activities such as exploration, navigation, and sleep. The hippocampus plays a crucial role in the brain’s ability to remember the past. Memory, Not Experience, Drives Theta Activity Prior to this study, it was believed that the external environment played a more important role in driving theta oscillations, said Arne Ekstrom, professor of cognition and neural systems at the UArizona Department of Psychology and senior author of the study. But Ekstrom and his collaborators found that memory generated in the brain is the main driver of theta activity. “Surprisingly, we found that theta oscillations in humans are more prevalent when someone is just remembering things, compared to experiencing events directly,” said lead study author Sarah Seger, a graduate student in the Department of Neuroscience. The results of the study could have implications for treating patients with brain damage and cognitive impairments, including patients who have experienced seizures, stroke, and Parkinson’s disease, Ekstrom said. Memory could be used to create stimulations from within the brain and drive theta oscillations, which could potentially lead to improvements in memory over time, he said. UArizona researchers collaborated on the study with researchers from the University of Texas Southwestern Medical Center in Dallas, including neurosurgeon Dr. Brad Lega and research technician Jennifer Kriegel. The researchers recruited 13 patients who were being monitored at the center in preparation for epilepsy surgery. As part of the monitoring, electrodes were implanted in the patient’s brains to detect occasional seizures. The researchers recorded the theta oscillations in the hippocampus of the brain. The patients participated in a virtual reality experiment, in which they were given a joystick to navigate to shops in a virtual city on a computer. When they arrived at the correct destination, the virtual reality experiment was paused. The researchers asked the participants to imagine the location at which they started their navigation and instructed them to mentally navigate the route they just passed through. The researchers then compared theta oscillations during initial navigation to participants’ subsequent recollection of the route. During the actual navigation process using the joystick, the oscillations were less frequent and shorter in duration compared to oscillations that occurred when participants were just imagining the route. So, the researchers conclude that memory is a strong driver of theta oscillations in humans. Harnessing Memory to Enhance Brain Function One way to compensate for impaired cognitive function is by using cognitive training and rehabilitation, Ekstrom said. “Basically, you take a patient who has memory impairments, and you try to teach them to be better at memory,” he said. In the future, Ekstrom is planning to conduct this research in freely walking patients as opposed to patients in beds and find how freely navigating compares to memory with regard to brain oscillations. “Being able to directly compare the oscillations that were present during the original experience, and during a later retrieval of that is a huge step forward in the field in terms of designing new experiments and understanding the neural basis of memory,” Seger said. Reference: “Memory-related processing is the primary driver of human hippocampal theta oscillations” by Sarah E. Seger, Jennifer L.S. Kriegel, Brad C. Lega and Arne D. Ekstrom, 18 July 2023, Neuron. DOI: 10.1016/j.neuron.2023.06.015 The study was funded by the National Institutes of Health.

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