Galvan Adriana, Hu Xing, Smith Yoland, Wichmann Thomas
Yerkes National Primate Research Center and School of Medicine, Department of Neurology, Emory University, Atlanta, Georgia 30329
Yerkes National Primate Research Center and.
J Neurosci. 2016 Mar 23;36(12):3519-30. doi: 10.1523/JNEUROSCI.4363-15.2016.
The role of the corticothalamic projection in the ventral motor thalamus remains poorly understood. Therefore, we studied the electrophysiological responses of neurons in the basal ganglia and cerebellar receiving-territories of the motor thalamus (BGMT and CbMT, respectively) using optogenetic activation of corticothalamic projections in awake rhesus macaques. After injections of viral vectors carrying the excitatory opsins ChR2 or C1V1 into the primary motor and premotor cortices of two monkeys, we used optrodes to light activate opsin-expressing neurons in cortex or their terminals in the thalamus while simultaneously recording the extracellular activity of neurons in the vicinity of the stimulation sites. As expected, light activation of opsins in the cerebral cortex evoked robust, short-latency increases in firing of cortical neurons. In contrast, light stimulation of corticothalamic terminals induced small-amplitude, long-latency increases and/or decreases of activity in thalamic neurons. In postmortem material, opsins were found to be expressed in cell bodies and dendrites of cortical neurons and along their corticothalamic projections. At the electron microscopic level, opsin labeling was confined to unmyelinated preterminal axons and small terminals that formed asymmetric synapses with dendrites of projection neurons or GABAergic interneurons in BGMT and CbMT and with neurons in the reticular thalamic nucleus. The morphological features of the transfected terminals, along with the long latency and complex physiological responses of thalamic neurons to their activation, suggest a modulatory role of corticothalamic afferents upon the primate ventral motor thalamus.
This study provides the first analysis of the physiological effects of cortical inputs on the activity of neurons in the primate ventral motor thalamus using light activation of opsin-containing corticothalamic terminals in awake monkeys. We found that selective light activation of corticothalamic terminals in contact with distal dendrites of thalamocortical neurons and GABAergic interneurons elicits complex patterns of slowly developing excitatory and inhibitory effects in thalamic neurons of the basal ganglia- and cerebellar-receiving regions of the motor thalamus. Our observations suggest a modulatory (instead of a "driver") role of the corticothalamic system in the primate ventral motor thalamus.
皮质丘脑投射在腹侧运动丘脑的作用仍知之甚少。因此，我们利用清醒恒河猴皮质丘脑投射的光遗传学激活，研究了运动丘脑的基底神经节和小脑接受区（分别为BGMT和CbMT）神经元的电生理反应。在向两只猴子的初级运动皮层和运动前区皮层注射携带兴奋性视蛋白ChR2或C1V1的病毒载体后，我们使用光电极对皮层中表达视蛋白的神经元或其丘脑终末进行光激活，同时记录刺激部位附近神经元的细胞外活动。正如预期的那样，大脑皮层中视蛋白的光激活引起了皮层神经元放电的强烈短潜伏期增加。相比之下，皮质丘脑终末的光刺激诱导丘脑神经元活动出现小幅度、长潜伏期的增加和/或减少。在死后材料中，发现视蛋白在皮层神经元的胞体和树突以及它们的皮质丘脑投射中表达。在电子显微镜水平上，视蛋白标记局限于无髓鞘的终末前轴突和小终末，这些终末在BGMT和CbMT中与投射神经元或GABA能中间神经元的树突以及丘脑网状核中的神经元形成不对称突触。转染终末的形态特征，以及丘脑神经元对其激活的长潜伏期和复杂生理反应，表明皮质丘脑传入纤维对灵长类动物腹侧运动丘脑具有调节作用。
本研究首次利用清醒猴子中含视蛋白的皮质丘脑终末的光激活，分析了皮质输入对灵长类动物腹侧运动丘脑神经元活动的生理影响。我们发现，与丘脑皮质神经元和GABA能中间神经元的远端树突接触的皮质丘脑终末的选择性光激活，在运动丘脑的基底神经节和小脑接受区的丘脑神经元中引发了缓慢发展的兴奋性和抑制性效应的复杂模式。我们的观察结果表明，皮质丘脑系统在灵长类动物腹侧运动丘脑中起调节（而非“驱动”）作用。
