Deconstruction of Vermal Cerebellum in Ramp Locomotion in Mice

Lyu, Chenfei; Yu, Chencen; Sun, Guanglong; Zhao, Yue; Cai, Ruolan; Sun, Hao; Wang, Xintai; Jia, Guoqiang; Fan, Lingzhu; Chen, Xi; Zhou, Lin; Shen, Ying; Gao, Lixia; Li, Xinjian

doi:10.1002/advs.202203665

Cited by 4 publications

(1 citation statement)

References 62 publications

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“…Engagement in locomotion on the runged treadmill elicits a significant increase in MLI activity (Fig. 4H) similar to what has been reported for walking on flat surfaces (Jelitai et al, 2016;Ozden et al, 2012) or walking on a slope (Lyu et al, 2022). In line with the fact that cerebellar control of movement is predominantly ipsilateral (Darmohray et al, 2019;Heffley et al, 2018;Lee et al, 2015), we found that most cells in the left simplex were tuned to ipsilateral front left paw events, also the hind left paw events were more often observed than hind right events (Figs.…”

Section: Discussionsupporting

confidence: 87%

Cerebellar interneuron activity is triggered by reach endpoint during learning of a complex locomotor task

Andrianarivelo,

Stein,

Gabillet

et al. 2023

Preprint

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Locomotion in complex environments depends on the precise timing and active control of single paw movements in order to adapt steps to surface structure and coordinate paws. Such motor control crucially depends on the cerebellum. In turn, cerebellar activity is reported to reflect limb movement kinematics, but how precise action timing in complex environments is controlled by the cerebellar circuit is currently unknown. To address this question, we developed LocoReach: a new task which combines continuous and discrete aspects of motor control by requiring mice to walk on a runged treadmill, where each step involves reaching for the next rung. Over several days of learning, mice became increasingly proficient at LocoReach, so that they made fewer, longer strides with faster swings and fewer missteps. We assessed the cerebellar role during LocoReach learning through electrophysiological recordings of molecular layer interneurons (MLIs), as they are thought to control the timing and gain of the cerebellar cortical output. When analyzing behaviorally-evoked responses in MLIs, we found sharp changes in activity around paw-specific transitions from swing to stance and vice versa. While most MLIs in the left simplex were preferentially modulated by the reach endpoint of the front left paw, a large proportion of cells additionally showed activity variations related to other paws or even multiple paws. Stronger firing rate modulations reflected longer strides made over learning, consistent with previous reports highlighting the role of the intermediate cerebellum in controlling reach endpoint precision. Our results provide the first demonstration that cerebellar inhibitory signals are tuned to specific events in the step cycle which can act as a powerful mechanism for the precise control of paw placements.

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Section: Discussionsupporting

confidence: 87%

Cerebellar interneuron activity is triggered by reach endpoint during learning of a complex locomotor task

Andrianarivelo,

Stein,

Gabillet

et al. 2023

Preprint

View full text Add to dashboard Cite

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Deconstruction of Vermal Cerebellum in Ramp Locomotion in Mice

Lyu

Sun

et al. 2022

Advanced Science

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The cerebellum is involved in encoding balance, posture, speed, and gravity during locomotion. However, most studies are carried out on flat surfaces, and little is known about cerebellar activity during free ambulation on slopes. Here, it has been imaged the neuronal activity of cerebellar molecular interneurons (MLIs) and Purkinje cells (PCs) using a miniaturized microscope while a mouse is walking on a slope. It has been found that the neuronal activity of vermal MLIs specifically enhanced during uphill and downhill locomotion. In addition, a subset of MLIs is activated during entire uphill or downhill positions on the slope and is modulated by the slope inclines. In contrast, PCs showed counter-balanced neuronal activity to MLIs, which reduced activity at the ramp peak. So, PCs may represent the ramp environment at the population level. In addition, chemogenetic inactivation of lobule V of the vermis impaired uphill locomotion. These results revealed a novel micro-circuit in the vermal cerebellum that regulates ambulatory behavior in 3D terrains.

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The Restoration of Social Defects in Schizophrenic Mice by Plant Exposure

Li,

Zhou

et al. 2024

Preprint

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Schizophrenia is a serious psychotic disorder caused by both individuals' genetic background and their living environment. However, how cognitive and negative symptoms can be treated is still a challenge since most anti-psychotic drugs are only effective for positive symptoms. Previous epidemic studies have demonstrated that plant exposure could decrease the risk of schizophrenia and shorten the length of psychiatric hospital admissions for patients. However, it is still unknown whether plant exposure could improve cognition-related defects in schizophrenia, with no related animal studies. In the present study, we first induced a schizophrenia mice model by giving mice long-term (2 weeks) injections of the antagonist of the NMDA receptor: MK801. We then raised the animals in environments containing plants (4 weeks) including Epipremnum aureum and rosemary, and tested their locomotive, anxious and social behaviors. We found that plant exposure did not change the locomotion behaviors of wild-type animals, but significantly reduced the schizophrenia-related social and anxious behaviors in the schizophrenic animals. In addition, we tested the expression of c-Fos in animals exposed to plants after social behavioral testing. We found that the deficits in c-Fos expression in both the hippocampus and prefrontal cortex were partially rescued after plant exposure. These results indicate plant exposure will be a new tool to improve the clinical deficits of schizophrenia.

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Deconstruction of Vermal Cerebellum in Ramp Locomotion in Mice

Cited by 4 publications

References 62 publications

Cerebellar interneuron activity is triggered by reach endpoint during learning of a complex locomotor task

Cerebellar interneuron activity is triggered by reach endpoint during learning of a complex locomotor task

Deconstruction of Vermal Cerebellum in Ramp Locomotion in Mice

The Restoration of Social Defects in Schizophrenic Mice by Plant Exposure

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