Reflex pathways in the control of intestinal motility

描述（由申请方提供）：结肠平滑肌张力和运动性的异常变化是GI疾病的病理指标。然而，肌张力，肠神经活动和推进之间的关系尚不清楚。兴奋性和抑制性神经递质的释放调节纵向（LM）和环形肌肉（CM）层的张力。通常不认识到肌肉张力本身可以改变肠神经系统中的活动。我们的新的初步研究结果表明，音调依赖和音调独立（拉伸激活）的运动模式存在，但这些运动活动是不同的近端和远端孤立的结肠。这些不同的运动模式将为我们提供一个重要的机会窗口，解剖出，第一次，音调依赖和独立的神经回路结肠运动活动的基础。我们证明，这些运动模式似乎是由两个不同的内在传感器/神经元：IPANS（AH-神经元），是敏感的肌肉紧张度和收缩和上升的中间神经元，其活动是拉伸依赖，但独立于肌肉紧张度。因此，ENS中的感觉传导类似于体神经系统中的感觉传导，其中高尔基体腱器官和肌梭分别提供关于肌肉张力和肌肉长度的互补信息。此外，我们发现，这两个神经元的感觉过程似乎位于CM，但不是LM。我们将使用离体豚鼠近端和远端结肠，以确定：AIM 1：拉伸如何激活肌张力依赖性和张力无关性神经反射通路，这些神经反射通路是近端和远端结肠推进活动的基础。 目的2：牵张运动反射时结肠周围LM细胞和肌间神经元的激活程度。目的3：LM或CM是否是大肠运动活动的感觉传导所必需的。目的4：研究肌间AH、S神经元和粘膜下神经元在结肠运动中的作用及其放电模式。将采用几种新的技术，包括：1）同时从LM或CM细胞和肌间或粘膜下神经元的细胞内记录。2)肠壁运动的视频成像。3)神经元和肌肉的钙成像。4)Dil逆行标记的机械敏感性上行中间神经元的细胞内记录。

DESCRIPTION (provided by applicant): Abnormal changes in colonic smooth muscle tone and motility are pathological indicators of GI disorders. However the relationship between muscle tone, enteric neural activity and propulsion is unclear. The release of excitatory and inhibitory neurotransmitters regulates tone of both the longitudinal (LM) and circular muscle (CM) layers. It is generally unappreciated that muscle tone itself can alter activity in the enteric nervous system. Our novel preliminary findings suggest that both tone dependent and tone independent (stretch activated) motility patterns exist, but these motor activities are different in proximal and distal isolated colon. These different motor patterns will provide us with an important window of opportunity to dissect out, for the first time, the tone dependent and independent neural circuitry underlying colonic motor activity. We demonstrate that these motor patterns appear to be regulated by two different intrinsic sensor/neurons: IPANS {AH-neurons) that are sensitive to muscle tone and contraction and ascending interneurons whose activity is stretch dependent but independent of muscle tone. Therefore, sensory transduction in the ENS is analogous to that in the somatic nervous system where Golgi tendon organs and muscle spindles provide complementary information regarding muscle tension and muscle length respectively. Furthermore, we show that the sensory processes of these two neurons appear to be located within the CM but not the LM. We will use the isolated guinea-pig proximal and distal colon, to determine: AIM 1: how stretch activates muscle tone dependent and tone independent neural reflex pathways that underlie propulsive activities in proximal and distal colon. AIM 2: the extent of activation of LM cells and myenteric neurons around the circumference of the colon during stretch induced motor reflexes. AIM 3: whether the LM or CM is necessary for sensory transduction underlying motor activities in the large intestine. AIM 4: the role and firing patterns of myenteric AH and S neurons and submucosal neurons in colonic motor activities. Several new techniques will be used, which indclude: 1) Simultaneous intracellular recordings from LM or CM cells and from myenteric or submucosal neurons. 2) Video imaging of movements of the gut wall. 3) Calcium imaging of neurons and muscle. 4) Intracellular recording from Dil retrogradely labeled mechanosensitive ascending interneurons.