HackMD論文分析：Peripersonal encoding of forelimb proprioception in the mouse somatosensory cortex
摘要：
Conscious perception of limb movements depends on proprioceptive neural responses in the somatosensory cortex. In contrast to tactile sensations, proprioceptive cortical coding is barely studied in the mammalian brain and practically non-existent in rodent research. To understand the cortical representation of this important sensory modality we developed a passive forelimb displacement paradigm in behaving mice and also trained them to perceptually discriminate where their limb is moved in space. We delineated the rodent proprioceptive cortex with wide-field calcium imaging and optogenetic silencing experiments during behavior. Our results reveal that proprioception is represented in both sensory and motor cortical areas. In addition, behavioral measurements and responses of layer 2/3 neurons imaged with two-photon microscopy reveal that passive limb movements are both perceived and encoded in the mouse cortex as a spatial direction vector that interfaces the limb with the body’s peripersonal space.
想解決的問題
該研究旨在了解哺乳動物大腦中重要的感覺模式 - 本體感覺的皮質編碼，尤其是在老鼠大腦中的表徵方式和空間感知。
使用的方法
該研究使用了被動性的前肢位移範式，訓練老鼠在空間中感知肢體的移動，並使用廣域鈣成像和光遺傳學靜默實驗來描繪老鼠本體感覺皮質。此外，研究還使用了雙光子顯微鏡成像來觀察第2/3層神經元的行為測量和反應，以揭示被動肢體運動在老鼠大腦皮質中的表徵方式和空間方向向量。
最終的成果
該研究的最終成果顯示，被動肢體運動可以在老鼠大腦皮質中被感知和編碼，本體感覺在感覺和運動皮質區域中都有表現，並被表徵為一個與身體周邊空間交互的空間方向向量。研究使用了廣域鈣成像、光遺傳學靜默實驗和雙光子顯微鏡成像等技術，描繪了老鼠本體感覺皮質。這些研究成果有助於深入了解哺乳動物大腦中的本體感覺編碼機制，並為未來的神經科學研究提供了重要參考。
關鍵字
proprioception, somatosensory cortex, mice
隨筆
Fig 2 介紹
在簡單的語言中，Fig. 2 在該論文中主要介紹了以下幾點：
Fig. 2a: 描述了實驗設置，這包括寬域成像系統（用於記錄大腦皮質的活動）和一種被稱為機械臂的設備，該設備被用來被動地移動老鼠的前肢。
Fig. 2b: 這是實驗的時間線。老鼠的前肢首先被移動到目標位置，然後在隨機的時間延遲之後返回到原點。這個過程被記錄下來，並與大腦活動的影像資料一起分析。
Fig. 2c: 這個圖顯示了當前肢被移動（本體感覺刺激）或爪子被振動（觸覺刺激）時，老鼠大腦的反應。結果顯示，前肢被移動時，老鼠的感覺和運動區域都被激活。而在觸覺刺激下，只有感覺區域被激活。
Fig. 2d: 這個圖顯示了本體感覺刺激和觸覺刺激對大腦皮質活動的影響，具體表現為活動高峰的位置。觸覺刺激引起的活動高峰位置在不同的老鼠之間是相當一致的，而本體感覺刺激引起的活動高峰位置則不太一致。
這些圖表大致上試圖告訴我們：在老鼠被動地移動前肢（本體感覺刺激）時，其大腦的感覺區域和運動區域都會被激活。而在爪子被振動（觸覺刺激）時，只有感覺區域被激活。這可能暗示本體感覺和觸覺在大腦中的處理可能有所不同。
首先我們先看到圖A，這裡描述了實驗的示意圖，上面使用 wide-field 的 camera，可以看到比較大面積的 鈣離子 活動，這裡的小鼠頭部被固定，他被訓練要抓住前方的機械臂，這個機械臂在實驗中會帶小鼠的右手往不同的方向，藉此可以研究本體感覺腦區中的 鈣離子活動。
First, let's turn our attention to Figure A, which illustrates the schematic of the experiment. Here, a wide-field camera was utilized, allowing us to observe a broad area of calcium activity. The mouse's head was fixed in position and it was trained to grasp the mechanical arm in front of it. During the experiment, this mechanical arm would guide the mouse's right hand in different directions, thereby enabling us to study the calcium activity within the proprioceptive regions of the brain.
再來是圖B ，說明了 trial 的 timeline，首先會有一個 Pre-stim baseline，這個時間會記錄一個鈣離子活動的 baseline，時間長度為2秒，接著機械臂快速會帶小鼠的手到8個不同的方向的位置，接著隨機的持續1-2秒，再將小鼠的手帶回到初始位置，這個隨機可以避免小鼠根據時間預期下一步的動作，這可以更準確的研究本體感覺。如果小鼠成功的完成實驗，那就給予水當獎勵，不然就吹風當作逞罰。
Moving on to Figure B, this illustrates the timeline of the trial. Initially, there is a 'Pre-stim baseline' period, where the baseline calcium activity is recorded for a duration of 2 seconds. Following this, the robotic arm swiftly moves the mouse's hand to one of eight different positions. Then, the hand is held in place for a randomly chosen duration of 1-2 seconds before being returned to the initial position. This random duration prevents the mouse from anticipating the next movement based on time, allowing for a more accurate study of proprioception. If the mouse successfully completes the experiment, it is rewarded with water; otherwise, it experiences a puff of air as a deterrent.
接著看到圖C ，左圖可以看到是實驗過程中，活動增強的區域，但是由於上述的實驗沒辦法區分來源是觸覺或本體感覺，所以作者設計了一個震動機械臂的實驗，這可以反映觸覺與鈣離子活動的關聯，也就是右圖，根據兩張圖的差異，我們可以看到顯著的區域差異，這個差異可以顯示本體感覺與鈣離子活動的關聯！
Next, we have Figure C. the left image shows the regions with enhanced calcium activity during the experiment. However, due to the inability of the aforementioned experiment to distinguish between tactile and proprioceptive sources, the authors designed an experiment with a vibrating mechanical arm. This can reflect the correlation between tactile stimulation and calcium activity, as shown in the right image. Based on the differences between the two images, we can observe significant regional disparities. These disparities can illustrate the relationship between proprioception and calcium activity.
最後我們看到圖D，這個圖顯示了本體感覺刺激和觸覺刺激對鈣離子活動的影響，有趣的是，鈣離子活動變化最大的區域也就是圖中的圓圈，紅色是觸覺刺激實驗，7隻老鼠的峰值區域十分接近，但是本體感覺的實驗中，鈣離子活動變化最大的區域較為分散，也就是藍色圓圈，但這兩種分布差異能得到的結論我不知道。
"Finally, we arrive at Figure D, which illustrates the influence of proprioceptive and tactile stimulations on calcium activity. Interestingly, the regions with the most significant changes in calcium activity, indicated by the circles in the image, show a distinct pattern. The red circles represent tactile stimulation experiments, and the peak regions of 7 mice are quite close to each other. However, in the proprioception experiments, the regions with the most significant changes in calcium activity are more dispersed, as shown by the blue circles. The conclusions that can be drawn from these distribution differences are beyond my current understanding."
