Powell Gregory L, Levine Richard B, Frazier Amanda M, Fregosi Ralph F
Departments of Physiology, The University of Arizona, Tucson, Arizona;
Departments of Physiology, The University of Arizona, Tucson, Arizona; Department of Neuroscience, The University of Arizona, Tucson, Arizona; and.
J Neurophysiol. 2015 Mar 15;113(6):1862-72. doi: 10.1152/jn.00838.2014. Epub 2014 Dec 30.
Smoothly graded muscle contractions depend in part on the precision and reliability of motoneuron action potential generation. Whether or not a motoneuron generates spikes precisely and reliably depends on both its intrinsic membrane properties and the nature of the synaptic input that it receives. Factors that perturb neuronal intrinsic properties and/or synaptic drive may compromise the temporal precision and the reliability of action potential generation. We have previously shown that developmental nicotine exposure (DNE) alters intrinsic properties and synaptic transmission in hypoglossal motoneurons (XIIMNs). Here we show that the effects of DNE also include alterations in spike-timing precision and reliability, and spike-frequency adaptation, in response to sinusoidal current injection. Current-clamp experiments in brainstem slices from neonatal rats show that DNE lowers the threshold for spike generation but increases the variability of spike-timing mechanisms. DNE is also associated with an increase in spike-frequency adaptation and reductions in both peak and steady-state firing rate in response to brief, square wave current injections. Taken together, our data indicate that DNE causes significant alterations in the input-output efficiency of XIIMNs. These alterations may play a role in the increased frequency of obstructive apneas and altered suckling strength and coordination observed in nicotine-exposed neonatal humans.
平滑分级的肌肉收缩部分取决于运动神经元动作电位产生的精确性和可靠性。运动神经元能否精确且可靠地产生动作电位,既取决于其内在膜特性,也取决于它所接收的突触输入的性质。干扰神经元内在特性和/或突触驱动的因素可能会损害动作电位产生的时间精确性和可靠性。我们之前已经表明,发育性尼古丁暴露(DNE)会改变舌下运动神经元(XIIMNs)的内在特性和突触传递。在此我们表明,DNE的影响还包括在响应正弦电流注入时,动作电位时间精确性和可靠性以及动作电位频率适应性的改变。对新生大鼠脑干切片进行的电流钳实验表明,DNE降低了动作电位产生的阈值,但增加了动作电位时间机制的变异性。DNE还与动作电位频率适应性增加以及在响应短暂方波电流注入时峰值和稳态放电率降低有关。综合来看,我们的数据表明DNE会导致XIIMNs的输入-输出效率发生显著改变。这些改变可能在尼古丁暴露的新生儿中观察到的阻塞性呼吸暂停频率增加以及吸吮强度和协调性改变中起作用。