Volen Center and Biology Department, Brandeis University, Waltham, Massachusetts 02454.
Volen Center and Biology Department, Brandeis University, Waltham, Massachusetts 02454
J Neurosci. 2018 Oct 17;38(42):8976-8988. doi: 10.1523/JNEUROSCI.2632-17.2018. Epub 2018 Sep 5.
Neurons in the central pattern-generating circuits in the crustacean stomatogastric ganglion (STG) release neurotransmitter both as a graded function of presynaptic membrane potential that persists in TTX and in response to action potentials. In the STG of the male crab , the modulators oxotremorine, tachykinin-related peptide Ia (CabTRP1a), red pigment concentrating hormone (RPCH), proctolin, TNRNFLRFamide, and crustacean cardioactive peptide (CCAP) produce and sustain robust pyloric rhythms by activating the same modulatory current (), albeit on different subsets of pyloric network targets. The muscarinic agonist oxotremorine, and the peptides CabTRP1a and RPCH elicited rhythmic triphasic intracellular alternating fluctuations of activity in the presence of TTX. Intracellular waveforms of pyloric neurons in oxotremorine and CabTRP1a in TTX were similar to those in the intact rhythm, and phase relationships among neurons were conserved. Although cycle frequency was conserved in oxotremorine and TTX, it was altered in CabTRP1a in the presence of TTX. Both rhythms were primarily driven by the pacemaker kernel consisting of the Anterior Burster and Pyloric Dilator neurons. In contrast, in TTX the circuit remained silent in proctolin, TNRNFLRFamide, and CCAP. These experiments show that graded synaptic transmission in the absence of voltage-gated Na current is sufficient to sustain rhythmic motor activity in some, but not other, modulatory conditions, even when each modulator activates the same ionic current. This further demonstrates that similar rhythmic motor patterns can be produced by qualitatively different mechanisms, one that depends on the activity of voltage-gated Na channels, and one that can persist in their absence. The pyloric rhythm of the crab stomatogastric ganglion depends both on spike-mediated and graded synaptic transmission. We activate the pyloric rhythm with a wide variety of different neuromodulators, all of which converge on the same voltage-dependent inward current. Interestingly, when action potentials and spike-mediated transmission are blocked using TTX, we find that the muscarinic agonist oxotremorine and the neuropeptide CabTRP1a sustain rhythmic alternations and appropriate phases of activity in the absence of action potentials. In contrast, TTX blocks rhythmic activity in the presence of other modulators. This demonstrates fundamental differences in the burst-generation mechanisms in different modulators that would not be suspected on the basis of their cellular actions at the level of the targeted current.
甲壳类动物口胃神经节（STG）中的中枢模式生成电路中的神经元以突触前膜电位的分级函数释放神经递质，该电位在 TTX 中持续存在，并对动作电位作出反应。在雄蟹的 STG 中，调节剂氧托米农、与速激肽相关的肽 Ia（CabTRP1a）、红色色素浓缩激素（RPCH）、普罗可林、TNRNFLRFamide 和甲壳动物心活性肽（CCAP）通过激活相同的调制电流（）产生并维持强大的幽门节律，尽管它作用于幽门网络目标的不同子集。在 TTX 存在的情况下，毒蕈碱激动剂氧托米农和肽 CabTRP1a 和 RPCH 引发了活动的有节奏的三相细胞内交替波动。在 TTX 中，氧托米农和 CabTRP1a 中的幽门神经元的细胞内波形与完整节律中的波形相似，并且神经元之间的相位关系得到了保留。尽管在氧托米农和 TTX 中，周期频率保持不变，但在 CabTRP1a 中，周期频率在 TTX 存在时发生了改变。这两种节律主要由由前爆发神经元和幽门扩张神经元组成的起搏器核心驱动。相比之下，在 TTX 中，在普罗可林、TNRNFLRFamide 和 CCAP 中，电路保持沉默。这些实验表明，在没有电压门控 Na 电流的情况下，分级突触传递足以维持某些但不是其他调节条件下的有节奏的运动活动，即使每种调节剂都激活相同的离子电流。这进一步表明，类似的节奏运动模式可以由不同的机制产生，一种依赖于电压门控 Na 通道的活性，另一种可以在其不存在的情况下持续存在。蟹 STG 的幽门节律既依赖于尖峰介导的和分级突触传递。我们使用各种不同的神经调节剂激活幽门节律，所有这些调节剂都集中在相同的电压依赖性内向电流上。有趣的是，当使用 TTX 阻断动作电位和尖峰介导的传递时，我们发现毒蕈碱激动剂氧托米农和神经肽 CabTRP1a 在没有动作电位的情况下维持有节奏的交替和适当的活动相位。相比之下，TTX 会阻止其他调节剂存在时的节律性活动。这表明不同调节剂中爆发生成机制存在根本差异，如果仅基于靶向电流水平的细胞作用，这些差异是不会被怀疑的。
