Multistability of bursting rhythms in a half-center oscillator and the protective effects of synaptic inhibition

IF 4.2 3区 医学 Q2 NEUROSCIENCES
Parker J. Ellingson, Yousif O. Shams, Jessica R. Parker, Ronald L. Calabrese, Gennady S. Cymbalyuk
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引用次数: 0

Abstract

For animals to meet environmental challenges, the activity patterns of specialized oscillatory neural circuits, central pattern generators (CPGs), controlling rhythmic movements like breathing and locomotion, are adjusted by neuromodulation. As a representative example, the leech heartbeat is controlled by a CPG driven by two pairs of mutually inhibitory interneurons, heart interneuron (HN) half-center oscillators (HCO). Experiments and modeling indicate that neuromodulation of HCO navigates this CPG between dysfunctional regimes by employing a co-regulating inverted relation; reducing Na+/K+ pump current and increasing hyperpolarization-activated (h-) current. Simply reducing pump activity or increasing h-current leads to either seizure-like bursting or an asymmetric bursting dysfunctional regime, respectively. Here, we demonstrate through modeling that, alongside this coregulation path, a new bursting regime emerges. Both regimes fulfill the criteria for functional bursting activity. Although the cycle periods and burst durations of these patterns are roughly the same, the new one exhibits an intra-burst spike frequency that is twice as high as the other. This finding suggests that neuromodulation could introduce additional functional regimes with higher spike frequency, and thus more effective synaptic transmission to motor neurons. We found that this new regime co-exists with the original bursting. The HCO can be switched between them by a short pulse of excitatory or inhibitory conductance. In this domain of coexisting functional patterns, an isolated cell model exhibits only one regime, a severely dysfunctional plateau-containing, seizure-like activity. This aligns with widely reported notion that deficiency of inhibition can cause seizures and other dysfunctional neural activities. We show that along the coregulation path of neuromodulation, the high excitability of the single HNs induced by myomodulin is harnessed by mutually inhibitory synaptic interactions of the HCO into the functional bursting pattern.
半中心振荡器猝发节奏的多稳定性和突触抑制的保护作用
为了让动物应对环境挑战,控制呼吸和运动等节律性运动的专门振荡神经回路--中央模式发生器(CPG)--的活动模式需要通过神经调节来调整。一个代表性的例子是,水蛭的心跳是由两对相互抑制的中间神经元--心脏中间神经元(HN)半中心振荡器(HCO)--驱动的 CPG 控制的。实验和建模表明,对 HCO 的神经调控通过采用一种共同调节的倒置关系(减少 Na+/K+ 泵电流和增加超极化激活(h-)电流),使 CPG 在功能失调状态之间游走。单纯降低泵活性或增加 h-电流会分别导致癫痫样猝发或非对称猝发功能障碍机制。在这里,我们通过建模证明,在这种核心调节途径的同时,还出现了一种新的猝发机制。这两种机制都符合功能性爆发活动的标准。虽然这些模式的周期和爆发持续时间大致相同,但新模式的爆发内尖峰频率是另一种模式的两倍。这一发现表明,神经调控可以引入更多具有更高尖峰频率的功能机制,从而更有效地向运动神经元进行突触传递。我们发现,这种新的机制与原有的突发性机制并存。通过一个短脉冲的兴奋或抑制传导,HCO 可以在两者之间切换。在这一功能模式共存的领域中,一个孤立的细胞模型只表现出一种机制,即严重的功能失调性高原、癫痫样活动。这与广泛报道的抑制不足可导致癫痫发作和其他功能失调的神经活动的观点一致。我们的研究表明,沿着神经调节的核心调节路径,肌球蛋白诱导的单个 HNs 的高兴奋性被 HCO 的相互抑制突触相互作用所利用,从而形成功能性猝发模式。
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来源期刊
CiteScore
7.90
自引率
3.80%
发文量
627
审稿时长
6-12 weeks
期刊介绍: Frontiers in Cellular Neuroscience is a leading journal in its field, publishing rigorously peer-reviewed research that advances our understanding of the cellular mechanisms underlying cell function in the nervous system across all species. Specialty Chief Editors Egidio D‘Angelo at the University of Pavia and Christian Hansel at the University of Chicago are supported by an outstanding Editorial Board of international researchers. This multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to researchers, academics, clinicians and the public worldwide.
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