Department of Chemical Physiology and Biochemistry, Oregon Health and Science University, Portland, OR, USA.
Department of Anesthesiology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
J Physiol. 2023 Apr;601(7):1247-1264. doi: 10.1113/JP284059. Epub 2023 Mar 3.
The sympathetic nervous system vitally regulates autonomic functions, including cardiac activity. Postganglionic neurons of the sympathetic chain ganglia relay signals from the central nervous system to autonomic peripheral targets. Disrupting this flow of information often dysregulates organ function and leads to poor health outcomes. Despite the importance of these sympathetic neurons, fundamental aspects of the neurocircuitry within peripheral ganglia remain poorly understood. Conventionally, simple monosynaptic cholinergic pathways from preganglionic neurons are thought to activate postganglionic sympathetic neurons. However, early studies suggested more complex neurocircuits may be present within sympathetic ganglia. The present study recorded synaptic responses in sympathetic stellate ganglia neurons following electrical activation of the pre- and postganglionic nerve trunks and used genetic strategies to assess the presence of collateral projections between postganglionic neurons of the stellate ganglia. Orthograde activation of the preganglionic nerve trunk, T-2, uncovered high jitter synaptic latencies consistent with polysynaptic connections. Pharmacological inhibition of nicotinic acetylcholine receptors with hexamethonium blocked all synaptic events. To confirm that high jitter, polysynaptic events were due to the presence of cholinergic collaterals from postganglionic neurons within the stellate ganglion, we knocked out choline acetyltransferase in adult noradrenergic neurons. This genetic knockout eliminated orthograde high jitter synaptic events and EPSCs evoked by retrograde activation. These findings suggest that cholinergic collateral projections arise from noradrenergic neurons within sympathetic ganglia. Identifying the contributions of collateral excitation to normal physiology and pathophysiology is an important area of future study and may offer novel therapeutic targets for the treatment of autonomic imbalance. KEY POINTS: Electrical stimulation of a preganglionic nerve trunk evoked fast synaptic transmission in stellate ganglion neurons with low and high jitter latencies. Retrograde stimulation of a postganglionic nerve trunk evoked direct, all-or-none action currents and delayed nicotinic EPSCs indistinguishable from orthogradely-evoked EPSCs in stellate neurons. Nicotinic acetylcholine receptor blockade prevented all spontaneous and evoked synaptic activity. Knockout of acetylcholine production in noradrenergic neurons eliminated all retrogradely-evoked EPSCs but did not change retrograde action currents, indicating that noradrenergic neurons have cholinergic collaterals connecting neurons within the stellate ganglion.
交感神经系统对自主功能至关重要，包括心脏活动。交感链神经节的节后神经元将信号从中枢神经系统传递到自主外周靶标。这种信息流的中断通常会使器官功能失调，并导致健康状况不佳。尽管这些交感神经元很重要，但外周神经节内的神经回路的基本方面仍知之甚少。传统上，认为节前神经元的简单单突触胆碱能途径激活节后交感神经元。然而，早期研究表明，交感神经节内可能存在更复杂的神经回路。本研究记录了电刺激节前和节后神经干后星状神经节神经元的突触反应，并使用遗传策略来评估星状神经节节后神经元之间是否存在侧支投射。节前神经干 T-2 的正向激活揭示了与多突触连接一致的高抖动突触潜伏期。六烃季铵对烟碱型乙酰胆碱受体的药理学抑制阻断了所有的突触事件。为了确认高抖动、多突触事件是由于星状神经节内节后神经元的胆碱能侧支存在，我们在成年去甲肾上腺素能神经元中敲除了胆碱乙酰转移酶。这种基因敲除消除了正向高抖动突触事件和逆行激活引起的 EPSC。这些发现表明，胆碱能侧支投射来自交感神经节内的去甲肾上腺素能神经元。确定侧支兴奋对正常生理学和病理生理学的贡献是未来研究的一个重要领域，并且可能为自主失衡的治疗提供新的治疗靶点。
刺激节前神经干可在星状神经节神经元中引发具有低抖动和高抖动潜伏期的快速突触传递。节后神经干的逆行刺激引发直接的、全或无的动作电流和延迟的烟碱型 EPSC，与星状神经元中正向引发的 EPSC 无法区分。烟碱型乙酰胆碱受体阻断阻止了所有自发性和诱发性突触活动。在去甲肾上腺素能神经元中敲除乙酰胆碱的产生消除了所有逆行引发的 EPSC，但不改变逆行动作电流，表明去甲肾上腺素能神经元具有连接星状神经节内神经元的胆碱能侧支。
