Pedunculopontine Chx10+ neurons control global motor arrest in mice

Abstract

Arrest of ongoing movements is an integral part of executing motor programs. Behavioral arrest may happen upon termination of a variety of goal-directed movements or as a global motor arrest either in the context of fear or in response to salient environmental cues. The neuronal circuits that bridge with the executive motor circuits to implement a global motor arrest are poorly understood. We report the discovery that the activation of glutamatergic Chx10-derived neurons in the pedunculopontine nucleus (PPN) in mice arrests all ongoing movements while simultaneously causing apnea and bradycardia. This global motor arrest has a pause-and-play pattern with an instantaneous interruption of movement followed by a short-latency continuation from where it was paused. Mice naturally perform arrest bouts with the same combination of motor and autonomic features. The Chx10-PPN-evoked arrest is different to ventrolateral periaqueductal gray-induced freezing. Our study defines a motor command that induces a global motor arrest, which may be recruited in response to salient environmental cues to allow for a preparatory or arousal state, and identifies a locomotor-opposing role for rostrally biased glutamatergic neurons in the PPN.

Modulation of pedunculopontine input to the basal ganglia relieves motor symptoms in Parkinsonian mice

“…Our results identify a population of glutamatergic neurons in the PPN that project to the SNr, control the locomotion by effective modulation of gait. A recent study has described a population of glutamatergic neurons in the PPN defined by expression of the transcription factor Chx10( 13 ). High frequency stimulation (40 Hz) of these neurons in the PPN resulted in motor arrest as well reduction of respiration and heart rate( 13 ) and suggested that these cells define a circuit for global motor arrest( 13 ).…”

“…A recent study has described a population of glutamatergic neurons in the PPN defined by expression of the transcription factor Chx10( 13 ). High frequency stimulation (40 Hz) of these neurons in the PPN resulted in motor arrest as well reduction of respiration and heart rate( 13 ) and suggested that these cells define a circuit for global motor arrest( 13 ). Low frequency stimulation was not tested, and the pathways that mediate changes in gait, respiration and heart rate were not examined.…”

“…Thus, targeted optogenetic activation of glutamatergic neurons in the CnF can initiate high speed movement from rest, but the neural circuits which select the type of gait engaged are not known ( 9–11 ). The role of the PPN is less clear, and stimulation of neurons within the PPN have shown mixed results with some studies reporting increases in movement( 10 ), some a reduction( 11, 12 ), or arrest of movement( 13 ) and others reporting no effect( 10 ). Functionally, ascending PPN projections are thought to initiate goal directed movement via the motor cortex( 2, 9, 14 ) while descending connections are thought to initiate motor arrest via the spinal CPGs( 13 ).…”

“…The role of the PPN is less clear, and stimulation of neurons within the PPN have shown mixed results with some studies reporting increases in movement( 10 ), some a reduction( 11, 12 ), or arrest of movement( 13 ) and others reporting no effect( 10 ). Functionally, ascending PPN projections are thought to initiate goal directed movement via the motor cortex( 2, 9, 14 ) while descending connections are thought to initiate motor arrest via the spinal CPGs( 13 ). However, the neurons in the PPN that control these different behaviours, or their targets are not known.…”

Pedunculopontine-stimulation obstructs hippocampal theta rhythm and halts movement

“…It is also seen for example, in rodents as a freezing behavior to a pain-conditioned response or looming threat 21 with an immediate need for silence and immobility. It was recently observed that a similar arrest of movement could be induced by optogenetic stimulation of a subset of glutamatergic neurons, the Chx10 cells 1,4 , in a nucleus in the caudal mesencephalon known as the PedunculoPontine Nucleus (PPN). Similar behavior was observed by stimulation of unidentified neurons in PPN both in mice 2 and rats 3 and reduced motor activity and long-lasting muscle tone in mice 22 and cats 23,24 .…”