Wheeler Diek W, Kullmann Paul H M, Horn John P
Department of Neurobiology, University of Pittsburgh School of Medicine, E1440 Biomedical Science Tower, Pittsburgh, PA 15261, USA.
J Neurophysiol. 2004 Nov;92(5):2659-71. doi: 10.1152/jn.00470.2004. Epub 2004 Jun 22.
Biological gain mechanisms regulate the sensitivity and dynamics of signaling pathways at the systemic, cellular, and molecular levels. In the sympathetic nervous system, gain in sensory-motor feedback loops is essential for homeostatic regulation of blood pressure and body temperature. This study shows how synaptic convergence and plasticity can interact to generate synaptic gain in autonomic ganglia and thereby enhance homeostatic control. Using a conductance-based computational model of an idealized sympathetic neuron, we simulated the postganglionic response to noisy patterns of presynaptic activity and found that a threefold amplification in postsynaptic spike output can arise in ganglia, depending on the number and strength of nicotinic synapses, the presynaptic firing rate, the extent of presynaptic facilitation, and the expression of muscarinic and peptidergic excitation. The simulations also showed that postsynaptic refractory periods serve to limit synaptic gain and alter postsynaptic spike timing. Synaptic gain was measured by stimulating dissociated bullfrog sympathetic neurons with 1-10 virtual synapses using a dynamic clamp. As in simulations, the threshold synaptic conductance for nicotinic excitation of firing was typically 10-15 nS, and synaptic gain increased with higher levels of nicotinic convergence. Unlike the model, gain in neurons sometimes declined during stimulation. This postsynaptic effect was partially blocked by 10 microM Cd2+, which inhibits voltage-dependent calcium currents. These results support a general model in which the circuit variations observed in parasympathetic and sympathetic ganglia, as well as other neural relays, can enable functional subsets of neurons to behave either as 1:1 relays, variable amplifiers, or switches.
生物增益机制在系统、细胞和分子水平上调节信号通路的敏感性和动力学。在交感神经系统中，感觉-运动反馈回路中的增益对于血压和体温的稳态调节至关重要。本研究展示了突触汇聚和可塑性如何相互作用以在自主神经节中产生突触增益，从而增强稳态控制。使用理想化交感神经元的基于电导的计算模型，我们模拟了节后神经元对突触前活动噪声模式的反应，发现神经节中突触后动作电位输出可出现三倍放大，这取决于烟碱型突触的数量和强度、突触前发放率、突触前易化程度以及毒蕈碱型和肽能兴奋的表达。模拟还表明，突触后不应期有助于限制突触增益并改变突触后动作电位的时间。通过使用动态钳以1 - 10个虚拟突触刺激分离的牛蛙交感神经元来测量突触增益。与模拟结果一样，引发动作电位的烟碱型兴奋的阈值突触电导通常为10 - 15 nS，且突触增益随更高水平的烟碱型汇聚而增加。与模型不同的是，神经元中的增益在刺激过程中有时会下降。这种突触后效应被10 microM Cd2 +部分阻断，Cd2 +可抑制电压依赖性钙电流。这些结果支持了一个通用模型，其中在副交感神经节和交感神经节以及其他神经中继中观察到的电路变化可使神经元功能亚群表现为1:1中继、可变放大器或开关。
