大鼠內側視丘核警醒功能的電生理研究

Abstract

內背側核(mediodorsal nucleus, MD) 及板內側核(intralaminar nuclei, IL)是內側視丘處理傷害性痛覺的核區之一。此外，臨床上腦傷病人失去意識的症狀凸顯出此腦區對於清醒功能的重要性。我們假設內側視丘較適於警覺功能並採用疼痛刺激-反應關係、不同大腦狀態下的疼痛刺激-反應關係、麻醉轉清醒、以及昏昏欲睡轉清醒四個實驗來探討內側視丘參與傷害性痛覺及覺醒的功能。由於適當的傷害性刺激對清醒動物的疼痛研究有關鍵性的影響，本論文第一個實驗主旨為定量分析雷射熱痛刺激。採用高速拍攝的紅外線熱像儀表現出短脈衝雷射在大鼠後腳掌表皮上造成的熱分佈，並利用熱傳導模型預測能興奮皮下傷害性感受器的雷射強度。第二個實驗利用埋設電極的大鼠探討在麻醉、清醒、及昏昏欲睡時雷射熱引起的刺激－反應關係。我們發現，當痛刺激給予在昏昏欲睡時，內側視丘的強度識別能力優於當刺激給予在清醒時。麻醉時則不具強度識別能力。昏昏欲睡時增強的強度識別能力可能由於內側視丘的警醒功能。第三個實驗利用麻醉動物探討其機械性痛刺激與熱痛刺激－反應關係。80%內側視丘神經元反應曲線呈現階梯形或鐘形，顯示內側視丘操作模式適於分辨傷害性刺激的發生與否，而不適於識別強度。第四個實驗利用埋設電極的大鼠探討神經活性與覺醒時間順序。我們發現最早的板內側核會領先內背側核及外側視丘核放電，且大部分的板內側核會領先覺醒的腦波。結果支持板內側核能引起覺醒。綜合以上結果，我們推論內背側核及板內側核具有覺醒的功能並參與痛覺警醒處理過程。

Mediodorsal (MD) and intralaminar (IL) thalamic nuclei are critical relays of nociception and pain in the medial thalamus (MT). Clinical cases implicate the importance of this area related to consciousness. The purpose of the present thesis is to test how MT neurons participate in nociception and arousal function. Four series of experiments were performed. Stimulus-response function (SRF) of MT neurons to noxious stimuli was done to test the hypothesis that MT neurons are better suited as an alarm system. To prepare an adequate noxious stimulus to free-moving animals, we used short-pulse CO2 laser. In Experiment 1, we first examined quantitatively this methodology. Ultra-fast infrared camera was used to capture the temporal and spatial distribution of heat over the skin surface induced by short-pulse CO2 laser. We also used mathematical modeling to predict the temporal and spatial pattern of activation of nociceptors in the epidermis. In Experiment 2, we used microelectrode-implanted rats to evaluate laser-heat evoked SRF of MD and IL neuronal activities under anesthetized, awake, and drowsy conditions. We found the coding ability of medial thalamic SRF was better when laser applied in drowsy state. Coding ability was flat in anesthetized state. These data suggest a function of noxious arousal. This property was absent in lateral thalamus. In Experiment 3, we used acute preparation of anesthetized rats to evaluate mechanical and thermal SRF of MD and IL neuronal activities. We found 80% MT units had a step-like or bell shaped SRF, suggesting their operational principle was better in distinguishing innocuous versus noxious stimuli rather than in coding intensity. In Experiment 4, we used microelectrode-implanted rats to evaluate sequence of arousal and neuronal firing in MD and IL. We found that neurons in IL led those in MD and lateral thalamus. Most thalamic activities led EEG arousal. The result suggested IL could participate in the induction of arousal. The series of studies jointly provide the functional evidence for medial thalamus involved in the arousal induction of nociception.