Zhang Yili, Golowasch Jorge
Federated Department of Biological Sciences, New Jersey Institute of Technology & Rutgers University, Newark, NJ, USA.
J Comput Neurosci. 2011 Nov;31(3):685-99. doi: 10.1007/s10827-011-0338-8. Epub 2011 May 15.
The pyloric network of decapods crustaceans can undergo dramatic rhythmic activity changes. Under normal conditions the network generates low frequency rhythmic activity that depends obligatorily on the presence of neuromodulatory input from the central nervous system. When this input is removed (decentralization) the rhythmic activity ceases. In the continued absence of this input, periodic activity resumes after a few hours in the form of episodic bursting across the entire network that later turns into stable rhythmic activity that is nearly indistinguishable from control (recovery). It has been proposed that an activity-dependent modification of ionic conductance levels in the pyloric pacemaker neuron drives the process of recovery of activity. Previous modeling attempts have captured some aspects of the temporal changes observed experimentally, but key features could not be reproduced. Here we examined a model in which slow activity-dependent regulation of ionic conductances and slower neuromodulator-dependent regulation of intracellular Ca(2+) concentration reproduce all the temporal features of this recovery. Key aspects of these two regulatory mechanisms are their independence and their different kinetics. We also examined the role of variability (noise) in the activity-dependent regulation pathway and observe that it can help to reduce unrealistic constraints that were otherwise required on the neuromodulator-dependent pathway. We conclude that small variations in intracellular Ca(2+) concentration, a Ca(2+) uptake regulation mechanism that is directly targeted by neuromodulator-activated signaling pathways, and variability in the Ca(2+) concentration sensing signaling pathway can account for the observed changes in neuronal activity. Our conclusions are all amenable to experimental analysis.
十足目甲壳动物的幽门神经网络会经历剧烈的节律性活动变化。在正常情况下，该网络产生低频节律性活动，这种活动必然依赖于来自中枢神经系统的神经调节输入的存在。当这种输入被去除（去神经支配）时，节律性活动就会停止。在持续没有这种输入的情况下，数小时后周期性活动会以整个网络的阵发性爆发形式恢复，随后转变为稳定的节律性活动，这种活动与对照（恢复）情况几乎无法区分。有人提出，幽门起搏器神经元中离子电导水平的活动依赖性修饰驱动了活动恢复的过程。以前的建模尝试捕捉到了实验中观察到的时间变化的一些方面，但关键特征无法重现。在这里，我们研究了一个模型，其中离子电导的缓慢活动依赖性调节和细胞内Ca(2+)浓度的较慢神经调节剂依赖性调节重现了这种恢复的所有时间特征。这两种调节机制的关键方面是它们的独立性和不同的动力学。我们还研究了变异性（噪声）在活动依赖性调节途径中的作用，并观察到它有助于减少否则会对神经调节剂依赖性途径施加的不切实际的限制。我们得出结论，细胞内Ca(2+)浓度的微小变化、一种直接由神经调节剂激活的信号通路靶向的Ca(2+)摄取调节机制以及Ca(2+)浓度传感信号通路中的变异性可以解释观察到的神经元活动变化。我们的结论都适合进行实验分析。
