Midbrain circuits that set locomotor speed and gait selection

Abstract

Summary Locomotion is a fundamental motor function common to the animal kingdom. It is executed episodically and adapted to behavioural needs including exploration, requiring slow locomotion, and escaping behaviour, necessitating faster speeds. The control of these functions originates in brainstem structures although the neuronal substrate(s) supporting them are debated. Here, we show in mice that speed/gait selection are controlled by glutamatergic excitatory neurons (GlutNs) segregated in two distinct midbrain nuclei: the Cuneiform Nucleus (CnF) and the Pedunculopontine Nucleus (PPN). GlutNs in each of those two regions are sufficient for controlling slower alternating locomotor behavior but only GlutNs in the CnF are necessary for high-speed synchronous locomotion. Additionally, PPN- and CnF-GlutNs activation dynamics and their input and output connectivity matrices support explorative and escape locomotion, respectively. Our results identify dual regions in the midbrain that act in common to select context dependent locomotor behaviours.

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.…”

“…Caggiano et al [2] went on to characterize the firing properties of glutamatergic neurons during locomotion at different speeds using extracellular recordings, showing that pedunculopontine nucleus neurons are more active at lower speeds, whereas cuneiform nucleus neurons are strongly recruited during fast locomotion. Further behavioral analyses have led the authors to propose a model in which the glutamatergic neurons of the cuneiform nucleus elicit fast locomotion to enable an escape response, whereas glutamatergic neurons of the pedunculopontine nucleus facilitate slow locomotor movements to favor an explorative behavior.…”

“…Caggiano et al [2] further examined the connectivity of excitatory neurons within the mesencephalic locomotor region, dissecting the presynaptic input to the anatomically distinct glutamatergic cuneiform nucleus and pedunculopontine nucleus populations. They found that the main inputs to glutamatergic neurons in the pedunculopontine nucleus originate from other midbrain structures, the basal ganglia, and several nuclei in the medulla.…”

“…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.…”

“…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.…”