Distinct Contributions of Mesencephalic Locomotor Region Nuclei to Locomotor Control in the Freely Behaving Mouse

Abstract

The mesencephalic locomotor region (MLR) has been initially identified as a supraspinal center capable of initiating and modulating locomotion. Whereas its functional contribution to locomotion has been widely documented throughout the phylogeny from the lamprey to humans, there is still debate about its exact organization. Combining kinematic and electrophysiological recordings in mouse genetics, our study reveals that glutamatergic neurons of the cuneiform nucleus initiate locomotion and induce running gaits, whereas glutamatergic and cholinergic neurons of the pedunculopontine nucleus modulate locomotor pattern and rhythm, contributing to slow-walking gaits. By initiating, modulating, and accelerating locomotion, our study identifies and characterizes distinct neuronal populations of this functional region important to locomotor command.

Locomotion Control: Brainstem Circuits Satisfy the Need for Speed

“…In their recent work, Caggiano et al [2] and Josset et al [3] further explored the anatomical and molecular heterogeneity of the mesencephalic locomotor region, highlighting the differential role of glutamatergic and cholinergic neurons within the cuneiform and pedunculopontine nuclei. They found that glutamatergic cuneiform nucleus neurons were able to drive the full range of locomotor gaits — walk, trot, bound and gallop — and speed.…”

“…To better understand how the mesencephalic locomotor region drives movement, Josset et al [3] took a closer look at muscle activity in resting or freely behaving mice following optogenetic activation of excitatory neurons within the cuneiform and pedunculopontine nuclei. The elicited muscle activity patterns were strongly dependent on whether the mouse was resting or walking (state-dependent), the step cycle phase (spinal gating of descending input) and the duration of photostimulation (temporal dynamics of neuronal recruitment).…”

“…The extensive characterization of medullary locomotor region projections performed by Caggiano et al [2] revealed very little input to the motor pools, implying downstream relay centers are needed for the muscle recruitment described by Josset et al [3]. Shefchyk et al [10] provided the first evidence localizing key mesencephalic locomotor region downstream effector circuits to the medulla by showing that cooling of the ventral medullary area halts locomotion elicited by electrical stimulation of the mesencephalic locomotor region.…”

“…Together, these three new studies [1–3] point to the presence of a dedicated glutamatergic cuneiform nucleus–lateral paragigantocellular nucleus circuit that can be used to elicit an escape response (Figure 1). Interestingly there appears to be a marked divergence in downstream targets of inhibitory versus excitatory neurons of the lateral paragigantocellular nucleus.…”

“…Novel viral and genetic tools have opened up new avenues for dissecting the cellular and anatomical features of the descending locomotor control circuitry. In three recent studies, the groups of Silvia Arber [1], Ole Kiehn [2] and Frederic Bretzner [3] (the last reported in this issue of Current Biology ) have identified broadly the neuronal populations in the mesencephalic locomotor region–medulla pathway that control the speed of stepping during locomotion.…”