Freely Behaving Mice Can Brake and Turn During Optogenetic Stimulation of the Mesencephalic Locomotor Region

Abstract

A key function of the mesencephalic locomotor region (MLR) is to control the speed of forward symmetrical locomotor movements. However, the ability of freely moving mammals to integrate environmental cues to brake and turn during MLR stimulation is poorly documented. Here, we investigated whether freely behaving mice could brake or turn, based on environmental cues during MLR stimulation. We photostimulated the cuneiform nucleus (part of the MLR) in mice expressing channelrhodopsin in Vglut2-positive neurons in a Cre-dependent manner (Vglut2-ChR2-EYFP) using optogenetics. We detected locomotor movements using deep learning. We used patch-clamp recordings to validate the functional expression of channelrhodopsin and neuroanatomy to visualize the stimulation sites. In the linear corridor, gait diagram and limb kinematics were similar during spontaneous and optogenetic-evoked locomotion. In the open-field arena, optogenetic stimulation of the MLR evoked locomotion, and increasing laser power increased locomotor speed. Mice could brake and make sharp turns (~90°) when approaching a corner during MLR stimulation in the open-field arena. The speed during the turn was scaled with the speed before the turn, and with the turn angle. Patch-clamp recordings in Vglut2-ChR2-EYFP mice show that blue light evoked short-latency spiking in MLR neurons. Our results strengthen the idea that different brainstem neurons convey braking/turning and MLR speed commands in mammals. Our study also shows that Vglut2-positive neurons of the cuneiform nucleus are a relevant target to increase locomotor activity without impeding the ability to brake and turn when approaching obstacles, thus ensuring smooth and adaptable navigation. Our observations may have clinical relevance since cuneiform nucleus stimulation is increasingly considered to improve locomotion function in pathological states such as Parkinson’s disease, spinal cord injury, or stroke.

Computational Modeling of Spinal Locomotor Circuitry in the Age of Molecular Genetics

“…Molecular genetic tools allow studying manipulations of neuronal components in awake, behaving animals [1,117,148,[154][155][156][157][158]. Thus, in contrast to reduced preparations, the spinal circuitry is embodied and interacts with the musculoskeletal system and the environment through motor output and afferent feedback.…”

Amygdala Underlies the Environment Dependency of Defense Responses Induced via Superior Colliculus

“…This suggests that the default response to the photostimulation is the retreat with backward locomotion and the amygdala is involved in forming the flight responses to the corner to immediately hide themselves, in addition to or by suppression of the retreat responses if the mice are placed in the closed environment. This may make sense because the CnF, the primary target of the SC defense pathway, has been considered to be the locomotor center or forming the central pattern generator for locomotion (Shik et al, 1966;Mori et al, 1978;Lee et al, 2014;van der Zouwen et al, 2021). Based on this assumption, we propose the circuit diagrams in Figure 5.…”

The neural bases of vertebrate motor behaviour through the lens of evolution

“…R. Soc. B 377: 20200521 of excitation to the locomotor networks is mediated by one particular part of the reticulospinal system-the lateral gigantocellular nucleus, although other nuclei are also known to contribute [10,11]. In both species, somatosensory information is conveyed via the dorsal columns and the dorsal column nuclei to the contralateral thalamic nuclei, and further to cortex [12,13].…”