Department of Neuroscience and Friedman Brain Institute , Icahn School of Medicine at Mount Sinai , One Gustave L. Levy Place , New York , New York 10029 , United States.
State Key Laboratory of Pharmaceutical Biotechnology, Advanced Institute for Life Sciences, School of Life Sciences , Nanjing University , Nanjing , Jiangsu 210093 , China.
ACS Chem Neurosci. 2018 Aug 15;9(8):1917-1927. doi: 10.1021/acschemneuro.7b00447. Epub 2018 Jan 24.
Neuropeptides are present in species throughout the animal kingdom and generally exert actions that are distinct from those of small molecule transmitters. It has, therefore, been of interest to define the unique behavioral role of this class of substances. Progress in this regard has been made in experimentally advantageous invertebrate preparations. We focus on one such system, the feeding circuit in the mollusc Aplysia. We review research conducted over several decades that played an important role in establishing that peptide cotransmitters are released under behaviorally relevant conditions. We describe how this was accomplished. For example, we describe techniques developed to purify novel peptides, localize them to identified neurons, and detect endogenous peptide release. We also describe physiological experiments that demonstrated that peptides are bioactive under behaviorally relevant conditions. The feeding system is like others in that peptides exert effects that are both convergent and divergent. Work in the feeding system clearly illustrates how this creates potential for behavioral flexibility. Finally, we discuss experiments that determined physiological consequences of one of the hallmark features of peptidergic modulation, its persistence. Research in the feeding system demonstrated that this persistence can change network state and play an important role in determining network output.
神经肽存在于动物界的各个物种中,通常发挥的作用与小分子递质不同。因此,定义这类物质的独特行为作用一直是人们关注的焦点。在实验上具有优势的无脊椎动物制剂方面,在这方面已经取得了进展。我们专注于这样一个系统,即软体动物海兔的摄食回路。我们回顾了几十年来的研究,这些研究在确定肽共递质是在与行为相关的条件下释放方面发挥了重要作用。我们描述了如何做到这一点。例如,我们描述了开发用于纯化新型肽、将其定位到已识别神经元并检测内源性肽释放的技术。我们还描述了证明在与行为相关的条件下肽具有生物活性的生理学实验。摄食系统与其他系统一样,肽的作用既有收敛性又有发散性。摄食系统的研究清楚地说明了这如何为行为灵活性创造了潜力。最后,我们讨论了确定肽调制的一个标志性特征——持续性的生理后果的实验。摄食系统的研究表明,这种持续性可以改变网络状态,并在确定网络输出方面发挥重要作用。