Mechanisms Mediating Motor Pattern Selection by Peptidergic Neurons

9309804 Nusbaum这项拟议工作的目标是了解肽能神经元如何调节调节行为的节律性活跃神经网络的活动。节律活跃的神经网络受到来自神经系统其他区域的调制输入的强烈影响，无论是脊椎动物还是无脊椎动物。最大的一类调节递质是神经肽，但到目前为止，我们关于神经肽如何调节神经网络活动的大部分知识都来自于沐浴应用研究。关于神经网络对单个肽能神经元的反应方式，可获得的信息很少。此外，洗澡和释放神经肽不一定会在神经网络中产生相同的反应，这有几个原因。这些原因包括观察到：(1)肽能神经元经常共同释放其他递质，(2)神经肽在沐浴时往往比神经释放时到达更多的受体，以及(3)不同浓度的肽可以引起定性不同的神经网络反应。这项建议的具体目标是(1)对洗浴应用研究作为肽能神经传递模型的效用提供更现实的评估，以及(2)了解具有相同肽递质的一组神经元如何以及为什么从相同的节律活跃的神经网络中引发不同的反应。该提案的具体目的是确定这些差异是否是由于这些原胆碱神经元具有不同的共同递质，受到细胞外定位的多肽酶的不同影响，释放不同量的原胆碱，和/或将原胆碱释放到神经桩内的不同区域。这些目标将通过多学科的方法来实现，包括细胞内和细胞外的电生理学、高效液相和生物化学以及激光扫描共聚焦显微镜，以研究三种已鉴定的原胆碱神经元对幽门和胃磨神经网络的影响方式。这项拟议的研究将提供有关神经释放的多肽影响神经网络活动的新的生理、生化和解剖学信息。这项研究还将首次深入了解使用神经肽的沐浴应用来研究神经网络对神经释放的多肽的反应的局限性。

9309804 Nusbaum The goal of this proposed work is to understand how peptidergic neurons modulate the activity of rhythmically active neural networks that mediate behaviors. Rhythmically active neural networks are strongly influenced by modulatory inputs from other regions of the nervous system, in both vertebrates and invertebrates. The largest class of modulatory transmitters is the neuropeptides, yet thus far most of our knowledge about how neuropeptides modulate neural network activity has come from bath- application studies. Little information is available regarding the ways in which neural networks respond to individual peptidergic neurons. Moreover, there are several reasons why bath-application and neural-release of a neuropeptide will not necessarily produce the same response in a neural network. These reasons include the observations that (1) peptidergic neurons often co-release other transmitters, (2) neuropeptides often reach more receptors when bath-applied than when neurally-released, and (3) different concentrations of a peptide can cause qualitatively different neural network responses. The specific goals of this proposal are to (1) provide a more realistic assessment of the utility of bath-application studies as a model for peptidergic neurotransmission, and (2) understand how and why a set of neurons that have the same peptide transmitter elicit different responses from the same rhythmically active neural networks. The specific aims of the proposal are to determine whether these differences are the result of these proctolin neurons having different co-transmitters, being differentially influenced by extracellularly- located peptidases, releasing different amount of proctolin, and/or releasing proctolin into different domains within the neuropil. These aims will be attained by using a multidisciplinary approach, including intra- and extracellular electrophysiology, HPLC- and bioassay-focussed biochemistry, and laser scanning confocal mi croscopy, to study the ways that three identified proctolin neurons influence the pyloric and gastric mill neural networks. This proposed study will provide novel physiological, biochemical and anatomical information about the means by which neurally- released peptides influence neural network activity. This study will also provide the first in-depth understanding of the limitations of using bath-application of neuropeptides to study neural network responses to neurally-released peptides.***