相對於傳統的有線方式，利用無線傳輸技術來擷取生理訊號提供了動物研究上相當多的優勢。一般來說，導線穿透皮膚可能會造成傷口的感染，且連接線也可能會被動物給損壞或者限制了動物的行動能力。然而，透過無線傳輸技術將可以在一個廣大的空間上對清醒且活動自由的動物進行生理訊號監測及電刺激。在本研究中，我們將無線生醫微系統應用在坐骨神經損傷的大鼠上，並利用阻抗量測方式來評估神經的再生情況；另外也將無線系統應用在回饋預期的學習研究上，並利用快速掃描循環伏安技術來偵測短暫的多巴胺訊號變化。

穿皮電刺激通常被應用在促進周邊神經的再生。然而，很少研究進行過長期監測神經再生的情況。在此研究的第一個部分中，我們以坐骨神經損傷的大鼠作為實驗模式，並利用植入式生醫微系統所產生的刺激電流來促進神經修復，且藉由紀錄隨時間變化的神經阻抗數值來評估神經再生的情形。為了能進行長時間的植入，我們利用經表皮的電磁耦合技術進行電力及數據的傳輸。在為期42天的動物實驗中，此植入式模組被放置在大鼠腹部的皮下，而環狀電極則包裹在具有8-mm間距的坐骨神經上。在術後的第8至21天中，第一組的動物藉由環狀電極來進行單相定電流的神經刺激，而第二組動物則沒有接受任何電刺激。在術後的第42天，具有神經再生的組別，其阻抗值從初始的數值增加到150%以上，而沒有神經再生的組別，其阻抗值只有增加113%。因此，神經再生組別的阻抗值上升將可以作為明顯功能恢復前的觀察方法。而在具有神經再生的組別當中，有接受電刺激的組別比沒有接受電刺激的組別產生了相對較高的髓鞘纖維密度(20686 vs. 11417 fiber/mm2)。因此，我們所發展的植入式生醫微系統已被證實對於利用長期電刺激來促進神經纖維生長，以及利用阻抗測量方式來評估隨時間變化的神經再生情形是一項有效的實驗工具。

快速掃描循環伏安法普遍地被用來監測短暫的多巴胺釋放，並常常用在有線的記錄與有限的動物行為實驗上。在此研究的第二個部分中，我們整合一個可監測腹側紋狀體多巴胺訊號的無線快速掃描循環伏安系統與一個可以產生雙相刺激電流並興奮多巴胺神經的電刺激器，並且將此整合系統應用於清醒且活動自由的老鼠上。此無線快速掃描循環伏安模組利用單向傳輸方式將測量到的多巴胺訊號傳至電腦主機端。為了減少電氣的干擾，光耦合器與各自的獨立電源被用來隔離快速掃描循環伏安系統與電刺激器。而此電刺激器則可經由紅外光控制並加以驅動。在系統驗證測試中，此無線模組與傳統的有線快速掃描循環伏安系統有著相似的效能，而且此無線模組對於老鼠的活動力並無太大的影響。在古柯鹼測試中，老鼠接受10 mg/kg古柯鹼注射的20分鐘後，電刺激所誘發的多巴胺分泌訊號增加了約230%左右。而在古典制約實驗的『維持階段(maintenance phase)』裡的連續50個試驗中，多巴胺訊號對於線索訊號的反應增加了60 nM，而電刺激所誘發的多巴胺濃度則從90 nM 降低至 50 nM。相反地，在『消退階段(extinction phase)』實驗中，多巴胺訊號對於線索訊號的反應則逐漸下降，而電刺激誘發的多巴胺濃度也完全被消除。在為期5個月的長期電刺激電極植入後，大腦的組織切片只呈現些微的損傷。因此，我們所發展的無線快速掃描循環伏安系統已被證實對於在活動自由老鼠的學習行為研究下的連續多巴胺監測是一項有效的實驗工具。

Physiological data collection using wireless transmission technique has many advantages over traditional wired approaches in animal studies. Usually, wire passing through skin might cause wound infection and the wire could be damaged by the animal and impede the animal movement. Furthermore, the physiological data monitoring and electrical stimulation can be performed via wireless transmission approach in an awake freely moving animal in a large space studies. In this study, we utilized the wireless biomicrosystems for assessing the condition of nerve regeneration via impedance measurement technique in injured sciatic nerve rat model as well as detecting phasic dopamine signal via fast-scan cyclic voltammtery (FSCV) technique in reward-predictive learning study.

Electrical stimulation is usually applied percutaneously for facilitating peripheral nerve regeneration. However, few studies have conducted long-term monitoring of the condition of nerve regeneration. The first part of this study implemented an implantable biomicrosystem for inducing pulse current for aiding nerve repair and monitoring the time-course changes of nerve impedance for assessing nerve regeneration in sciatic nerve injury rat model. For long-term implantation, a transcutaneous magnetic coupling technique was adopted for power and data transmission. For in vivo study, the implanted module was placed in the rat’s abdomen and the cuff electrode was wrapped around an 8-mm sciatic nerve gap of the rat for nerve impedance measurement for 42 days. One group of animals received monophasic constant current via the cuff electrode and a second group had no stimulation between days 8 to 21. The nerve impedance increased to above 150% of the initial value in the nerve regeneration groups with and without stimulation whereas the group with no nerve regeneration increased to only 113% at day 42. The impedance increase in nerve regeneration groups can be observed before evident functional recovery. Also, the nerve regeneration group that received electrical stimulation had relatively higher myelinated fiber density than that of no stimulation group, 20686 vs. 11417 fiber/mm2. The developed implantable biomicrosystem is proven to be a useful experimental tool for long-term stimulation in aiding nerve fiber growth as well as impedance assessment for understanding the time-course changes of nerve regeneration.

FSCV is commonly used to monitor phasic dopamine release, which is usually performed using tethered recording and for limited types of animal behavior. The second part of this study integrated a wireless FSCV system for monitoring the dopamine signal in the ventral striatum with an electrical stimulator that induces biphasic current to excite dopaminergic neurons in awake freely moving rats. The measured dopamine signals are unidirectionally transmitted from the wireless FSCV module to the host unit. To reduce electrical artifacts, an optocoupler and a separate power are applied to isolate the FSCV system and electrical stimulator, which can be activated by an infrared controller. In the validation test, the wireless backpack system has similar performance in comparison with conventional wired system and it does not significantly affect the locomotor activity of rat. In the cocaine administration test, the maximum electrically elicited dopamine signals increased to around 230% of the initial value 20 min after the injection of 10 mg/kg cocaine. In a classical conditioning test, the dopamine signal in response to a cue increased to around 60 nM over 50 successive trials while the electrically evoked dopamine concentration decreased from about 90 nM to 50 nM in the maintenance phase. In contrast, the cue-evoked dopamine concentration progressively decreased and the electrically evoked dopamine was eliminated during the extinction phase. In the histological evaluation, there was little damage to brain tissue after 5 months chronic implantation of stimulating electrode. The developed wireless FSCV system is proven to be a useful experimental tool for the continuous monitoring of dopamine levels during animal learning behavior studies of freely moving rats.

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