Functional Mapping of Medial Thalamic Projections in Rat Using MRI

• Main Authors: Pai-Feng Yang, 楊白峯
• Other Authors: Jyh-Horng Chen
• Format: Others
• Language: en_US
• Published: 2011
• Online Access: http://ndltd.ncl.edu.tw/handle/42589555829919424454

博士 === 國立臺灣大學 === 電機工程學研究所 === 99 === Pain is an unpleasant sensory and emotional experience and has significant influence on our normal function and quality of life. Therefore, it is important to understand pain mechanisms so that treatment of pain can be improved. In recent years, two MRI techniques are developed for mapping activation and connection patterns in specific brain circuits. The first one combines the blood oxygen level dependence (BOLD) responses and direct brain stimulation; and the other one is the manganese enhancement magnetic resonance imaging (MEMRI). In this dissertation, we used these methodologies to investigate the function and connection of the thalamic projections of the rat. In the first experiment, we analyzed the BOLD activation patterns in the forebrain through direct electrical stimulation of the ventroposterior nuclei (VP) and the medial dorsal nuclei (MD) of the thalamus. A flexible MR-compatible polyimide-based microelectrode array was implanted in the VP or the MD in α-chloralose anesthetized rats. Electrical stimulation was used to activate the VP or MD. BOLD responses were found in many forebrain targets. The ipsilateral forelimb region of the primary somatosensory cortex (S1) was most prominently activated after VP stimulation. Strongest activations occurred at 3 Hz. The threshold intensity was low (50 μA) but maximal response was reached at 100 μA. In contrast, direct MD stimulation revealed major activated areas in the ipsilateral anterior cingulate cortex (ACC). The best frequency of stimulus was 9-12 Hz. Increasing either intensity or frequency of stimulation produced graded increase in BOLD responses. We also found negative BOLD responses in the CPu both with MD and VP stimulation. In addition, c-Fos positive neurons following VP or MD stimulation were totally distinct. VP stimulation elicited few c-Fos labeled neurons in the ipsilateral S1. In contrast, MD stimulation produced numerous c-Fos positive neurons in the ACC and other forebrain regions. The differential BOLD and c-Fos responses induced by VP versus MD stimulation may indicate a fundamental difference in the synaptic mechanism of the medial and the lateral thalamic pain pathways. In the second experiment, we studied the nociceptive medial thalamus projection in rats by activity-dependent MEMRI. Rats under urethane and a-chloralose anesthesia were microinjected with manganese chloride (MnCl2, 120mmol/L, iontophoretically with a 5-μA current for 15 min) into the right medial thalamus, centered on MD. Innocuous (at 50-μA intensity and 0.2 ms pulse duration) or noxious (at 5-mA intensity and 2 ms pulse duration) electrical stimuli were applied through a pair of needles in the left forepaw pads once every 6 s for 5 h. Enhanced transport of Mn2+ were found in the ACC, mid-cingulate cortex, retrosplenial cortex, ventral medial caudate-putamen, nucleus accumbens, and amygdala in the noxious-stimulated group. Enhancements in the ACC, mid-cingulate cortex, ventral medial caudate-putamen, nucleus accumbens, and amygdala, but not the retrosplenial cortex, were attenuated by an intraperitoneal injection of morphine (5 mg/kg initially and 1 mg/kg/h infusion, intraperitoneal). These results indicate that a combination of MEMRI with activity-induced manganese-dependent contrast is useful for delineating functional connections in the pain pathway. In summary, this dissertation has successfully demonstrated the potential of direct brain stimulation fMRI and MEMRI in the study of the connectivity and function of nociceptive processing in the brain.