A recent study by Goni-Erro et al (2023) in Nature Neuroscience has shed light on a fascinating phenomenon: the neural control of global motor arrest. From the cessation of goal-directed actions to a broader motor arrest in response to fear or environmental cues, this complex behavior involves an intricate set of neuronal pathways. This recent study reveals that the activation of glutamatergic Chx10-derived neurons within the pedunculopontine nucleus (PPN) is the key orchestrator of global motor arrest, along with the accompanying cardiopulmonary effects.
The study, which combines anatomical, physiological, and behavioral approaches, demonstrates that the activation of Chx10 neurons in the PPN of mice induces a pause-and-play pattern of motor arrest. Upon optogenetic activation, ongoing movements come to an instantaneous halt, accompanied by apnea (temporary cessation of breathing) and bradycardia (reduced heart rate). Interestingly, this unique pattern of motor arrest exhibits a rapid offset, followed by a brief latency before the resumption of movement from where it paused. Mice themselves naturally demonstrate these arrest patterns, aligning with the concept that Chx10-PPN-evoked arrests are triggered by important environmental cues. Unlike other forms of motor arrest such as freezing, this distinctive pattern sets it apart and underlines its novelty.
The experimental setup of the cardiopulmonary portion involved the implantation of emka easyTEL-S-ETA telemetry sensors for electrocardiography (ECG) recordings, enabling the monitoring of heart rate in freely moving mice expressing ChR2 (a light-sensitive protein) in the PPN or vlPAG (ventrolateral periaqueductal gray). emka & SCIREQ whole-body plethysmography (WBP), modified to suit optogenetic experiments, allowed respiratory activity monitoring. The telemetry ECG recordings along with respiratory activity monitoring, allowed simultaneous tracking of cardiac and respiratory activity within the same IOX Software during various behavioral sessions.
Activation of Chx10-PPN neurons led to a significant reduction in respiratory rate, with some trials resulting in complete apnea during stimulation. Heart rate also experienced a mild reduction, especially towards the end of the stimulation. These findings highlight the multifaceted effects of Chx10-PPN neuron activation, shedding light on its role in regulating not only motor behavior but also autonomic functions like respiration and heart rate. Interestingly, the study also showed that similar behavioral patterns, including motor and autonomic features, occurred naturally in mice during baseline conditions without experimental manipulation, suggesting these patterns might be elicited by inherent triggers.
These findings hold potential implications for Parkinson’s disease (PD), a neurodegenerative disorder that involves the PPN. The study’s insights into the distinct roles of glutamatergic neurons in the PPN highlight potential avenues for deep brain stimulation in PD treatment. By targeting specific glutamatergic populations, researchers could potentially refine therapeutic strategies and enhance outcomes for patients.
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