Mohammadalinejad Ghazaleh, Afsharipour Babak, Yacyshyn Alex, Duchcherer Jennifer, Bashuk Jack, Bennett Erin, Pearcey Gregory E P, Negro Francesco, Quinlan Katharina A, Bennett David J, Gorassini Monica A
Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada.
Neuroscience and Mental Health Institute, University of Alberta, Edmonton, AB, Canada.
J Physiol. 2024 May;602(9):2061-2087. doi: 10.1113/JP285756. Epub 2024 Mar 30.
Motoneuron properties and their firing patterns undergo significant changes throughout development and in response to neuromodulators such as serotonin. Here, we examined the age-related development of self-sustained firing and general excitability of tibialis anterior motoneurons in a young development (7-17 years), young adult (18-28 years) and adult (32-53 years) group, as well as in a separate group of participants taking selective serotonin reuptake inhibitors (SSRIs, aged 11-28 years). Self-sustained firing, as measured by ΔF, was larger in the young development (∼5.8 Hz, n = 20) compared to the young adult (∼4.9 Hz, n = 13) and adult (∼4.8 Hz, n = 8) groups, consistent with a developmental decrease in self-sustained firing mediated by persistent inward currents (PIC). ΔF was also larger in participants taking SSRIs (∼6.5 Hz, n = 9) compared to their age-matched controls (∼5.3 Hz, n = 26), consistent with increased levels of spinal serotonin facilitating the motoneuron PIC. Participants in the young development and SSRI groups also had higher firing rates and a steeper acceleration in initial firing rates (secondary ranges), consistent with the PIC producing a steeper acceleration in membrane depolarization at the onset of motoneuron firing. In summary, both the young development and SSRI groups exhibited increased intrinsic motoneuron excitability compared to the adults, which, in the young development group, was also associated with a larger unsteadiness in the dorsiflexion torque profiles. We propose several intrinsic and extrinsic factors that affect both motoneuron PICs and cell discharge which vary during development, with a time course similar to the changes in motoneuron firing behaviour observed in the present study. KEY POINTS: Neurons in the spinal cord that activate muscles in the limbs (motoneurons) undergo increases in excitability shortly after birth to help animals stand and walk. We examined whether the excitability of human ankle flexor motoneurons also continues to change from child to adulthood by recording the activity of the muscle fibres they innervate. Motoneurons in children and adolescents aged 7-17 years (young development group) had higher signatures of excitability that included faster firing rates and more self-sustained activity compared to adults aged ≥18 years. Participants aged 11-28 years of age taking serotonin reuptake inhibitors had the highest measures of motoneuron excitability compared to their age-matched controls. The young development group also had more unstable contractions, which might partly be related to the high excitability of the motoneurons.
运动神经元的特性及其放电模式在整个发育过程中以及对血清素等神经调质的反应中会发生显著变化。在这里，我们研究了年轻发育期（7 - 17岁）、青年期（18 - 28岁）和成年期（32 - 53岁）组中胫骨前肌运动神经元的自发放电和一般兴奋性与年龄相关的发育情况，以及另一组服用选择性5-羟色胺再摄取抑制剂（SSRIs，年龄11 - 28岁）的参与者的情况。通过ΔF测量的自发放电，年轻发育期组（约5.8Hz，n = 20）比青年期组（约4.9Hz，n = 13）和成年期组（约4.8Hz，n = 8）更大，这与持续性内向电流（PIC）介导的自发放电的发育性降低一致。服用SSRIs的参与者（约6.5Hz，n = 9）的ΔF也比年龄匹配的对照组（约5.3Hz，n = 26）更大，这与脊髓血清素水平升高促进运动神经元PIC一致。年轻发育期组和SSRI组的参与者也有更高的放电率，并且初始放电率的加速更陡峭（二级范围），这与PIC在运动神经元放电开始时使膜去极化的加速更陡峭一致。总之，与成年人相比，年轻发育期组和SSRI组均表现出运动神经元内在兴奋性增加，在年轻发育期组中，这也与背屈扭矩曲线中更大的不稳定性相关。我们提出了几个影响运动神经元PIC和细胞放电的内在和外在因素，这些因素在发育过程中会发生变化，其时间进程与本研究中观察到的运动神经元放电行为的变化相似。要点：脊髓中激活肢体肌肉的神经元（运动神经元）在出生后不久兴奋性会增加，以帮助动物站立和行走。我们通过记录它们所支配肌肉纤维的活动，研究了人类踝部屈肌运动神经元的兴奋性从儿童到成年是否也会持续变化。7 - 17岁儿童和青少年（年轻发育期组）的运动神经元具有更高的兴奋性特征，包括比≥18岁的成年人更快的放电率和更多的自发放电活动。与年龄匹配的对照组相比，11 - 28岁服用血清素再摄取抑制剂的参与者运动神经元兴奋性的测量值最高。年轻发育期组的收缩也更不稳定，这可能部分与运动神经元的高兴奋性有关。
