NJIT, Newark, New Jersey 07102.
NJIT, Newark, New Jersey 07102
eNeuro. 2024 Sep 10;11(9). doi: 10.1523/ENEURO.0167-24.2024. Print 2024 Sep.
Ionic current levels of identified neurons vary substantially across individual animals. Yet, under similar conditions, neural circuit output can be remarkably similar, as evidenced in many motor systems. All neural circuits are influenced by multiple neuromodulators, which provide flexibility to their output. These neuromodulators often overlap in their actions by modulating the same channel type or synapse, yet have neuron-specific actions resulting from distinct receptor expression. Because of this different receptor expression pattern, in the presence of multiple convergent neuromodulators, a common downstream target would be activated more uniformly in circuit neurons across individuals. We therefore propose that a baseline tonic (non-saturating) level of comodulation by convergent neuromodulators can reduce interindividual variability of circuit output. We tested this hypothesis in the pyloric circuit of the crab, Multiple excitatory neuropeptides converge to activate the same voltage-gated current in this circuit, but different subsets of pyloric neurons have receptors for each peptide. We quantified the interindividual variability of the unmodulated pyloric circuit output by measuring the activity phases, cycle frequency, and intraburst spike number and frequency. We then examined the variability in the presence of different combinations and concentrations of three neuropeptides. We found that at mid-level concentration (30 nM) but not at near-threshold (1 nM) or saturating (1 µM) concentrations, comodulation by multiple neuropeptides reduced the circuit output variability. Notably, the interindividual variability of response properties of an isolated neuron was not reduced by comodulation, suggesting that the reduction of output variability may emerge as a network effect.
在不同个体中，已鉴定神经元的离子电流水平有很大差异。然而，在相似的条件下，神经回路的输出可以非常相似，许多运动系统都证明了这一点。所有的神经回路都受到多种神经调质的影响，这些神经调质通过调节相同的通道类型或突触，为其输出提供了灵活性。这些神经调质的作用往往重叠，通过调节相同的通道类型或突触，但由于受体表达的不同，它们对神经元有特定的作用。由于这种不同的受体表达模式，在存在多种会聚神经调质的情况下，一个共同的下游靶点在个体间的回路神经元中会更均匀地被激活。因此，我们提出，会聚神经调质的基础紧张（非饱和）调节水平可以降低回路输出的个体间变异性。我们在螃蟹的幽门神经回路中测试了这一假设，多个兴奋性神经肽会聚到同一个电压门控电流中激活这个回路，但不同的幽门神经元亚群有针对每种神经肽的受体。我们通过测量无调制幽门回路输出的活动相位、周期频率、爆发内尖峰的数量和频率来量化未调制幽门回路输出的个体间变异性。然后，我们研究了在存在三种神经肽的不同组合和浓度的情况下的变异性。我们发现，在中水平浓度（30 nM）但不是在近阈值浓度（1 nM）或饱和浓度（1 μM）下，多种神经肽的共调节降低了回路输出的变异性。值得注意的是，共调节并没有降低单个神经元反应特性的个体间变异性，这表明输出变异性的降低可能是一种网络效应。
