Functional coupling of the mesencephalic locomotor region and V2a reticulospinal neurons driving forward locomotion

Abstract

Locomotion in vertebrates relies on high brain centers converging onto the mesencephalic locomotor region (MLR). How the MLR recruits brainstem reticulospinal neurons (RSNs) to initiate locomotion is incompletely understood due to the challenge of recording these cells in vivo. To tackle this question, we leveraged the transparency and genetic accessibility of larval zebrafish. In this model organism, we uncovered the locus of the MLR as a small region dorsal to the locus coeruleus containing glutamatergic and cholinergic neurons. MLR stimulations reliably elicited forward bouts of controlled duration and speed. We find that the MLR elicits forward locomotion by recruiting V2a RSNs in the pontine and retropontine regions, and gradually in the medulla. Remarkably, recruited V2a RSNs in the medulla act as maintain cells encoding speed of forward locomotion. Altogether, our study reveals that the MLR recruits genetically-identified reticulospinal neurons in the medulla to control the kinematics of exploration.

Granger causality analysis for calcium transients in neuronal networks: challenges and improvements

“…Remarkably, we also detected strong driver neurons (Fig. 9A-C, left ) in the locus of the right MLR centered in rhombomere 1 ([38], Fig. 9B, left ).…”

“…Upstream of command neurons lies a critical high motor center that has been identified by electrical stimulations across multiple vertebrate species and is referred to as the mesencephalic locomotor region, or MLR [49]. We recently identified, functionally and anatomically, the locus of the MLR in larval zebrafish [38]. We therefore investigated the GC links across three ventral and horizontal planes where numerous command neurons are located in the caudal hindbrain [47, 48]: the reference plane analyzed in Fig.…”

“…Second, we apply our improved GC analysis to infer information flow from large neuronal populations in the brainstem of larval zebrafish performing optomotor response [34]. In the context of large populations of neurons, we show that our method is able to reveal that motor-correlated neurons within the recently-identified mesencephalic locomotor region in [38] drive the activity of downstream neurons in the reticular formation.…”

Early midbrain sensorimotor pathway is involved in the timely initiation and direction of swimming in the hatchling Xenopus laevis tadpole

“…The midbrain is an integral part of the survival brain network, and its role has been found to influence behavioral motor actions by projecting onto other parts of the brainstem, which in turn modulate CPG circuit activity in the spinal cord (Koutsikou et al, 2014;Koutsikou et al, 2015;Koutsikou et al, 2017;Arber and Costa, 2018;Ferreira-Pinto et al, 2018;Grillner and El Manira, 2020;Arber and Costa, 2022). In particular, the locomotor command systems in the midbrain (MLR: mesencephalic locomotor region), initially identified in cats (Shik et al, 1966;Shik et al, 1969), are conserved within the vertebrate lineage and play a multifaceted role in the control of locomotion (Ryczko and Dubuc, 2013;Grillner and El Manira, 2020;Carbo-Tano et al, 2022). Additionally, the descending circuitry of the midbrain nucleus of the medial longitudinal fascicle (nMLF) is the origin of the commands that regulate steering and posture during locomotion in zebrafish larvae (Severi et al, 2014;Thiele et al, 2014;Wang and McLean, 2014).…”

An early midbrain sensorimotor pathway is involved in the timely initiation and direction of swimming in the hatchling Xenopus laevis tadpole

“…The midbrain is an integral part of the survival brain network, and its role has been found to influence behavioral motor actions by projecting onto other parts of the brainstem, which in turn modulate CPG circuit activity in the spinal cord ( Koutsikou et al, 2014 , 2015 , 2017 ; Arber and Costa, 2018 , 2022 ; Ferreira-Pinto et al, 2018 ; Grillner and El Manira, 2020 ). In particular, the locomotor command systems in the midbrain (MLR: mesencephalic locomotor region), initially identified in cats ( Shik et al, 1966 , 1969 ), are conserved within the vertebrate lineage and play a multifaceted role in the control of locomotion ( Ryczko and Dubuc, 2013 ; Grillner and El Manira, 2020 ; Carbo-Tano et al, 2022 ). Additionally, the descending circuitry of the midbrain nucleus of the medial longitudinal fascicle (nMLF) is the origin of the commands that regulate steering and posture during locomotion in zebrafish larvae ( Severi et al, 2014 ; Thiele et al, 2014 ; Wang and McLean, 2014 ).…”