Carp Jonathan S, Tennissen Ann M, Chen Xiang Yang, Wolpaw Jonathan R
Laboratory of Neurons System Disorder, Wadsworth Center, New York State Department of Health, Albany, NY 12201-0509, USA.
J Neurophysiol. 2006 Oct;96(4):1718-27. doi: 10.1152/jn.00470.2006. Epub 2006 Jul 12.
Rats, monkeys, and humans can alter the size of their spinal stretch reflex and its electrically induced analog, the H-reflex (HR), when exposed to an operant conditioning paradigm. Because this conditioning induces plasticity in the spinal cord, it offers a unique opportunity to identify the neuronal sites and mechanisms that underlie a well-defined change in a simple behavior. To facilitate these studies, we developed an HR operant conditioning protocol in mice, which are better suited to genetic manipulation and electrophysiological spinal cord study in vitro than rats or primates. Eleven mice under deep surgical anesthesia were implanted with tibial nerve stimulating electrodes and soleus and gastrocnemius intramuscular electrodes for recording ongoing and stimulus-evoked EMG activity. During the 24-h/day computer-controlled experiment, mice received a liquid reward for either increasing (up-conditioning) or decreasing (down-conditioning) HR amplitude while maintaining target levels of ongoing EMG and directly evoked EMG (M-responses). After 3-7 wk of conditioning, the HR amplitude was 133 +/- 7% (SE) of control for up-conditioning and 71 +/- 8% of control for down-conditioning. HR conditioning was successful (i.e., > or =20% change in HR amplitude in the appropriate direction) in five of six up-conditioned animals (mean final HR amplitude = 139 +/- 5% of control HR for successful mice) and in four of five down-conditioned animals (mean final HR amplitude = 63 +/- 8% of control HR for successful mice). These effects were not attributable to differences in the net level of motoneuron pool excitation, stimulation strength, or distribution of HR trials throughout the day. Thus mice exhibit HR operant conditioning comparable with that observed in rats and monkeys.
当大鼠、猴子和人类处于操作性条件反射范式下时,它们能够改变脊髓牵张反射的大小及其电诱发类似物H反射(HR)。由于这种条件反射能在脊髓中诱导可塑性,它为识别简单行为中明确变化背后的神经元位点和机制提供了独特的机会。为了便于开展这些研究,我们在小鼠中开发了一种HR操作性条件反射方案,相比于大鼠或灵长类动物,小鼠更适合进行基因操作和体外脊髓电生理研究。11只处于深度手术麻醉状态的小鼠被植入胫神经刺激电极以及比目鱼肌和腓肠肌肌内电极,用于记录持续的和刺激诱发的肌电图活动。在每天24小时的计算机控制实验中,小鼠在保持持续肌电图和直接诱发肌电图(M反应)目标水平的同时,因增加(上调条件反射)或降低(下调条件反射)HR幅度而获得液体奖励。经过3 - 7周的条件反射训练后,上调条件反射组的HR幅度为对照组的133±7%(标准误),下调条件反射组为对照组的71±8%。6只上调条件反射的动物中有5只成功实现了HR条件反射(即HR幅度在适当方向上有≥20%的变化,成功小鼠的最终平均HR幅度 = 对照组HR的139±5%),5只下调条件反射的动物中有4只成功(成功小鼠的最终平均HR幅度 = 对照组HR的63±8%)。这些效应并非归因于运动神经元池兴奋的净水平、刺激强度或全天HR试验分布的差异。因此,小鼠表现出与大鼠和猴子中观察到的类似的HR操作性条件反射。