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Ventromedial Thalamus-Projecting DCN Neurons Modulate Associative Sensorimotor Responses in Mice

Neuroscience Bulletin 2022年第5期38卷 459-473页

作者： Jie Zhang Hao Chen Li-Bin Zhang Rong-Rong Li Bin Wang Qian-Hui Zhang Liu-Xia Tong Wei-Wei Zhang Zhong-Xiang Yao Bo Hu Department of Physiology College of Basic Medical SciencesArmy Medical UniversityChongqing 400038China Experimental Center of Basic Medicine College of Basic Medical SciencesArmy Medical UniversityChongqing 400038China 3948th Hospital of PLA Wusu 833300China College of Basic Medical Sciences Army Medical UniversitySquadron 15Battalion 5Chongqing 400038China Department of Foreign Language College of Basic Medical SciencesArmy Medical UniversityChongqing 400038China Brain and Intelligence Research Key Laboratory of Chongqing Education Commission Army Medical UniversityChongqing 400038China

The deep cerebellar nuclei(DCN)integrate various inputs to the cerebellum and form the final cerebellar outputs critical for associative sensorimotor learning.However,the functional relevance of distinct neuronal subpopulations within the DCN remains poorly understood.Here,we examined a subpopulation of mouse DCN neurons whose axons specifically project to the ventromedial(Vm)thalamus(DCNVm neurons),and found that these neurons represent a specific subset of DCN units whose activity varies with trace eyeblink conditioning(tEBC),a classical associative sensorimotor learning task.Upon conditioning,the activity of DCNVm neurons signaled the performance of conditioned eyeblink responses(CRs).Optogenetic activation and inhibition of the DCNVm neurons in well-trained mice amplified and diminished the CRs,respectively.Chemogenetic manipulation of the DCNVm neurons had no effects on non-associative motor coordination.Furthermore,optogenetic activation of the DCNVm neurons caused rapid elevated firing activity in the cingulate cortex,a brain area critical for bridging the time gap between sensory stimuli and motor execution during tEBC.Together,our data highlights DCNVm neurons’function and delineates their kinematic parameters that modulate the strength of associative sensorimotor responses.

关键词： deep cerebellar nuclei Ventromedial thalamus Trace eyeblink conditioning Sensorimotor learning

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Neuronal Activity in the Cerebellum During the Sleep-Wakefulness Transition in Mice

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Neuroscience Bulletin 2020年第8期36卷 919-931页

作者： Li-Bin Zhang Jie Zhang Meng-Jia Sun Hao Chen Jie Yan Fen-Lan Luo Zhong-Xiang Yao Ya-Min Wu Bo Hu Department of Physiology College of Basic Medical SciencesArmy Medical UniversityChongqing 400038China State Key Laboratory of Trauma Bums and Combined InjuryDaping Hospital/Research Institute of SurgeryArmy Medical UniversityChongqing 400042China Squadron 10 Battalion 3College of Basic Medical SciencesArmy Medical UniversityChongqing 400038China

cerebellar malfunction can lead to sleep disturbance such as excessive daytime sleepiness,suggesting that the cerebellum may be involved in regulating sleep and/or wakefulness.However,understanding the features of cerebellar regulation in sleep and wakefulness states requires a detailed characterization of neuronal activity within this area.By performing multiple-unit recordings in mice,we showed that Purkinje cells(PCs)in the cerebellar cortex exhibited increased firing activity prior to the transition from sleep to wakefulness.Notably,the increased PC activity resulted from the inputs of lowfrequency non-PC units in the cerebellar cortex.Moreover,the increased PC activity was accompanied by decreased activity in neurons of the deep cerebellar nuclei at the nonrapid eye-movement sleep-wakefulness transition.Our results provide in vivo electrophysiological evidence that the cerebellum has the potential to actively regulate the sleep-wakefulness transition.

关键词： Sleep Wakefulness Multiple-unit recording Purkinje cell deep cerebellar nuclei

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A cerebellar inhibitory signal for the regulation of sleep-wakefulness cycle

A cerebellar inhibitory signal for the regulation of sleep-w...

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中国睡眠研究会第十一届全国学术年会

作者： Bo Hu Li-Bin Zhang Jie Zhang Army Medical University

The cerebellum is a critical component of the CSN, involved in motor control and motor learning. However, patients suffering from cerebellar disorders induce not only motor deficits, but also non-motor symptoms such as increased daytime sleepiness. Vice versa, patients suffering primary sleep disorders such as daytime sleepiness are often accompanied by a decreased cerebellar volume. These data support the notion that the cerebellum might be involved in regulating sleep and wakefulness. Nevertheless, the neural mechanisms underlying this involvement remain largely unclear. Here, we examined a genetically tractable population of neurons in the mouse deep cerebellar nuclei（DCN）, whose axon fibers specifically project to the ventral lateral thalamus（VL）. We show that these neurons are composed of GABAergic（～50%）, Glycinergic（～25%） and Glutamatergic（～25%） neurons in the DCN. Therefore, most of the VL-projected DCN neurons are inhibitory units. Intriguingly, the inhibitory VL-projected DCN neurons also recurrently innervate in the cerebellar cortex. Immnohistochemmical staining reveal that the nucleocortical fiber terminals formed filopodia-like protrusions in the vicinity of Purkinje cell（PC） layer in the cerebellar cortex, indicating these fibers preferentially target the PCs. Indeed, optogenetic inhibition of the VL-projected DCN neurons disinhibits the PCs in the cerebellar cortex, which thereafter cause widespread inhibition in the DCN. Vice versa, optogenetic stimulation of the VL-projected DCN neurons induces rapid inhibition of the PCs, which results in widespread excitation in the DCN. It turns out that the inhibitory VL-projected DCN neurons can bi-directionally modulate the activities of PCs in the cerebellar cortex. In contrast, optogenetic activation of VL/VM-projected glutamatergic DCN neurons fails to induce widespread excitation in the DCN. Moreover, optogenetic activation of the VL-projected DCN neurons can provide an internal amplification of the outputs from the cerebellar cortex, as evidenced by th

关键词： deep cerebellar nuclei Ventral lateral thalamus Purkinje cell Sleep Wakefulness Multiple units recording Optogenetics Chemogenetics

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