Glutamatergic neurons of the gigantocellular reticular nucleus shape locomotor pattern and rhythm in the freely behaving mouse.

Maxime Lemieux,Frederic Bretzner

doi:10.1371/journal.pbio.2003880

Abstract

Because of their intermediate position between supraspinal locomotor centers and spinal circuits, gigantocellular reticular nucleus (GRN) neurons play a key role in motor command. However, the functional contribution of glutamatergic GRN neurons in initiating, maintaining, and stopping locomotion is still unclear. Combining electromyographic recordings with optogenetic manipulations in freely behaving mice, we investigate the functional contribution of glutamatergic brainstem neurons of the GRN to motor and locomotor activity. Short-pulse photostimulation of one side of the glutamatergic GRN did not elicit locomotion but evoked distinct motor responses in flexor and extensor muscles at rest and during locomotion. Glutamatergic GRN outputs to the spinal cord appear to be gated according to the spinal locomotor network state. Increasing the duration of photostimulation increased motor and postural tone at rest and reset locomotor rhythm during ongoing locomotion. In contrast, photoinhibition impaired locomotor pattern and rhythm. We conclude that unilateral activation of glutamatergic GRN neurons triggered motor activity and modified ongoing locomotor pattern and rhythm.

Highlights

Locomotion results from an interplay between the spinal circuit that generates locomotor pattern and rhythm, the sensory inputs from the peripheral afferents that shape motor responses, and the supraspinal descending inputs from the brainstem that send the locomotor command
Two types of optical probes were inserted above the gigantocellular reticular nucleus (GRN): single fibers of 100 μm in diameter or arrays of 3 fibers each spaced by 200 μm (S1 Fig, n = 6 mice for single fibers and n = 10 for arrays)
Combining EMG recordings with unilateral optogenetic manipulations enabled us to dissect the functional contribution of glutamatergic neurons of the GRN to motor and locomotor activity in the resting and walking mouse

Summary

Introduction

Locomotion results from an interplay between the spinal circuit that generates locomotor pattern and rhythm, the sensory inputs from the peripheral afferents that shape motor responses, and the supraspinal descending inputs from the brainstem that send the locomotor command. The firing pattern of reticular and reticulospinal neurons of the gigantocellular reticular nucleus (GRN) is in phase with locomotor activity [6,7,8]; firing increases while walking uphill (pitch tilt), during left or right roll tilt [9], or while stepping over obstacles during locomotion [10]. Glutamatergic GRN neurons in motor control no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Combining electromyographic (EMG) recordings with unilateral optogenetic manipulations, we evaluated the necessity and sufficiency of glutamatergic GRN neurons to initiate, maintain, and/or stop motor and locomotor activity in the freely behaving mouse. Short-pulse photostimulation (10 ms) increased motor tone in the resting mouse and modified locomotor activity according to the phase of the step cycle in the walking mouse, contributing to shaping locomotor pattern. Our findings reveal that glutamatergic GRN neurons, as a descending excitatory pathway, play a key role in motor control and locomotion

Results

Discussion

Ethics statement