The role of intraspinal sensory neurons in the control of quadrupedal locomotion

From swimming to walking and flying, animals have evolved specific locomotor strategies to thrive in different habitats. All types of locomotion depend on integration of motor commands and sensory information to generate precise movements. Cerebrospinal fluid-contacting neurons (CSF-cN) constitute a vertebrate sensory system that monitors CSF composition and flow. In fish, CSF-cN modulate swimming activity in response to changes in pH and bending of the spinal cord, yet their role in higher vertebrates remains unknown. We used mouse genetics to study their function in quadrupedal locomotion and found that CSF-cN are directly integrated into spinal motor circuits by forming connections with motor neurons and premotor interneurons. Elimination of CSF-cN selectively perturbs the accuracy of foot placement required for skilled movements at the balance beam and horizontal ladder. These results identify an important role for mouse CSF-cN in adaptive motor control and indicate that this sensory system evolved a novel function from lower vertebrates to accommodate the biomechanical requirements of terrestrial locomotion.

Distal Humeral Morphology Indicates Locomotory Divergence in Extinct Giant Kangaroos

Previous studies of the morphology of the humerus in kangaroos showed that the shape of the proximal humerus could distinguish between arboreal and terrestrial taxa among living mammals, and that the extinct “giant” kangaroos (members of the extinct subfamily Sthenurinae and the extinct macropodine genus Protemnodon) had divergent humeral anatomies from extant kangaroos. Here, we use 2D geometric morphometrics to capture the shape of the distal humerus in a range of extant and extinct marsupials and obtain similar results: sthenurines have humeral morphologies more similar to arboreal mammals, while large Protemnodon species (P. brehus and P. anak) have humeral morphologies more similar to terrestrial quadrupedal mammals. Our results provide further evidence for prior hypotheses: that sthenurines did not employ a locomotor mode that involved loading the forelimbs (likely employing bipedal striding as an alternative to quadrupedal or pentapedal locomotion at slow gaits), and that large Protemnodon species were more reliant on quadrupedal locomotion than their extant relatives. This greater diversity of locomotor modes among large Pleistocene kangaroos echoes studies that show a greater diversity in other aspects of ecology, such as diet and habitat occupancy.

The role of V3 neurons in speed-dependent interlimb coordination during locomotion in mice

Speed-dependent interlimb coordination allows animals to maintain stable locomotion under different circumstances. We have previously demonstrated that a subset of spinal V3 neurons contributes to stable locomotion by mediating mutual excitation between left and right lumbar rhythm generators (RGs). Here, we expanded our investigation to the V3 neurons involved in ascending long propriospinal interactions (aLPNs). Using retrograde tracing, we revealed a subpopulation of lumbar V3 aLPNs with contralateral cervical projections. V3OFF mice, in which all V3 neurons were silenced, had a significantly reduced maximal locomotor speed, were unable to move using stable trot, gallop, or bound, and predominantly used lateral-sequence walk. To understand the functional roles of V3 aLPNs, we adapted our previous model of spinal circuitry controlling quadrupedal locomotion (Danner et al., 2017), by incorporating diagonal V3 aLPNs mediating inputs from each lumbar RG to the contralateral cervical RG. The updated model reproduces our experimental results and suggests that locally projecting V3 neurons, mediating left–right interactions within lumbar and cervical cords, promote left–right synchronization necessary for gallop and bound, whereas the V3 aLPNs promote synchronization between diagonal fore and hind RGs necessary for trot. The model proposes the organization of spinal circuits available for future experimental testing.

Unusual Quadrupedal Locomotion in Rat during Recovery from Lumbar Spinal Blockade of 5-HT7 Receptors

Coordination of four-limb movements during quadrupedal locomotion is controlled by supraspinal monoaminergic descending pathways, among which serotoninergic ones play a crucial role. Here we investigated the locomotor pattern during recovery from blockade of 5-HT7 or 5-HT2A receptors after intrathecal application of SB269970 or cyproheptadine in adult rats with chronic intrathecal cannula implanted in the lumbar spinal cord. The interlimb coordination was investigated based on electromyographic activity recorded from selected fore- and hindlimb muscles during rat locomotion on a treadmill. In the time of recovery after hindlimb transient paralysis, we noticed a presence of an unusual pattern of quadrupedal locomotion characterized by a doubling of forelimb stepping in relation to unaffected hindlimb stepping (2FL-1HL) after blockade of 5-HT7 receptors but not after blockade of 5-HT2A receptors. The 2FL-1HL pattern, although transient, was observed as a stable form of fore-hindlimb coupling during quadrupedal locomotion. We suggest that modulation of the 5-HT7 receptors on interneurons located in lamina VII with ascending projections to the forelimb spinal network can be responsible for the 2FL-1HL locomotor pattern. In support, our immunohistochemical analysis of the lumbar spinal cord demonstrated the presence of the 5-HT7 immunoreactive cells in the lamina VII, which were rarely 5-HT2A immunoreactive.