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Motor responses in one leg to sensory stimulation of the contralateral leg have been named “crossed reflexes” and are extensively investigated in cats and humans. Despite this effort, a circuit-level understanding of the crossed reflexes has remained missing. In mice, advances in molecular genetics enabled insights into the “commissural spinal circuitry” that ensures coordinated leg movements during locomotion. Despite some common features between the commissural spinal circuitry and the circuit for the crossed reflexes, the degree to which they overlap has remained obscure. Here, we describe excitatory crossed reflex responses elicited by electrically stimulating the common peroneal nerve that mainly innervates ankle flexor muscles and the skin on anterolateral aspect of the hind leg. Stimulation of the peroneal nerve with low current intensity evoked low-amplitude motor responses in the contralateral flexor and extensor muscles. At higher current strengths, stimulation of the same nerve evoked stronger and more synchronous responses in the same contralateral muscles. In addition to the excitatory crossed reflex pathway indicated by muscle activation, we demonstrate the presence of an inhibitory crossed reflex pathway, which was modulated when the motor pools were active during walking. The results are compared with the crossed reflex responses initiated by stimulating proprioceptors from extensor muscles and cutaneous afferents from the posterior part of the leg. We anticipate that these findings will be essential for future research combining the in vivo experiments presented here with mouse genetics to understand crossed reflex pathways at the network level in vivo. NEW & NOTEWORTHY Insights into the mechanisms of crossed reflexes are essential for understanding coordinated leg movements that maintain stable locomotion. Advances in mouse genetics allow for the selective manipulation of spinal interneurons and provide opportunities to understand crossed reflexes. Crossed reflexes in mice, however, are poorly described. Here, we describe crossed reflex responses in mice initiated by stimulation of the common peroneal nerve, which serves as a starting point for investigating crossed reflexes at the cellular level.

SUMMARYTo achieve smooth motor performance in a rich and changing sensory environment, motor outputs must be constantly updated in response to sensory feedback. Although proprioception and cutaneous information are known to modulate motor output, it is unclear whether they work together in the spinal cord to shape complex motor actions such as locomotion. Here we identify the medial deep dorsal horn as a “hot zone” of convergent proprioceptive and cutaneous input for locomotion. Due to increased responsiveness to sensory input, inhibitory interneurons in the medial deep dorsal horn area are preferentially recruited in locomotion. To study inhibitory interneurons in this area, we utilize an intersectional genetic strategy to isolate and ablate a population of parvalbumin-expressing glycinergic interneurons in the medial deep dorsal horn (dPVs). Using histological and electrophysiological methods we find that dPVs integrate convergent proprioceptive and cutaneous input while targeting diffuse ventral horn motor networks. dPV ablation paired with behavioral testing and EMG recordings reveals a role for dPVs in the timing and magnitude of muscle recruitment, controlling step-cycle transition, kinematics, and limb coordination in a state and phase-dependent manner. Together, our results suggest that convergent sensory inputs work in concert to coordinate the activity of dPVs, and in-turn regulate motor output in a contextually relevant manner.HighlightsInhibitory interneurons in the medial deep dorsal horn (mDDH), functionally represented by a large glycinergic PV expressing subpopulation (dPVs), receive convergent input from cutaneous receptors and proprioceptors and are preferentially recruited during locomotion.While dPVs diffusely target motor networks, the temporal dynamics of their activity is regulated by incoming inputs, suggesting a role in modulation of motor output timing.Ablation of dPVs alters stance-to-swing transition and step frequency during high-speed locomotion, likely to result from loss of sensory mediated muscle inhibition.Ablation of dPVs alters joint kinematics at the transition from stance-to-swing, likely to result from loss of sensory mediated muscle amplitude attenuation.

The occurrence and the fate of 18 ozonation by-products (OBPs) (17 different aldehydes and bromate) were studied over one year in two Canadian drinking water systems. This is the first and only study reporting the occurrence of all these non-halogenated aldehydes (NON-HALs) and haloacetaldehydes (HALs) simultaneously, based on the multi-point monitoring of water in full-scale conditions from source to distribution network. In general, the application of both post-ozonation and liquid chlorine contributed to the formation of OBPs (aldehydes and bromate). NON-HALs were present in higher concentrations than HALs. Formaldehyde, acetaldehyde, glyoxal and methylglyoxal were the most common forms of NON-HALs in the two water systems that were studied. Chloral hydrate (CH), the hydrated form of trichloroacetaldehyde, was the most dominant HAL observed. The nature of the organic matter and the water temperature proved to be important parameters for explaining the variability of aldehydes. Summer and autumn (warm seasons) were more favorable for the formation of chloral hydrate and bromate. The highest concentrations of NON-HALs were observed in spring.

Developing strategies to identify the origins of contaminants in watersheds is crucial for source water protection. The use of multiple tracers improves the ability to identify contamination events originating from various land use activities. The objective of this study was to evaluate the use of acesulfame and chloride as co-tracers to represent the impact of pollution originating from wastewater and road de-icing on water quality in a municipal drinking water source. The study included a two-year sampling and water quality analysis program in numerous locations within a drinking water reservoir comprising a lake (upstream) and a river (downstream) which supply raw water to a municipal water treatment plant. Results showed that the spatial variability of acesulfame and chloride within the watershed of the lake-river systems depends on the location of contaminant sources, mainly municipal wastewater and septic tank discharges (for acesulfame) and the presence of small tributaries of the lake and river (for chloride). Temporal variability of the tracers under study differed according to the sampling location and was mainly affected by seasonal conditions. Correlation analyses between the two tracers in lake and river waters (in terms of concentrations and loads) made it possible to pinpoint the probable origins of contamination. The assessment of the spatio-temporal variability of these co-tracers within the lake-river watersheds allowed for the delineation of priority intervention zones as a decision-making tool for municipal authorities in improving drinking water source protection.

Down syndrome cell adherence molecule (DSCAM) contributes to the normal establishment and maintenance of neural circuits. Whereas there is abundant literature regarding the role of DSCAM in the neural patterning of the mammalian retina, less is known about motor circuits. Recently, DSCAM mutation has been shown to impair bilateral motor coordination during respiration, thus causing death at birth. DSCAM mutants that survive through adulthood display a lack of locomotor endurance and coordination in the rotarod test, thus suggesting that the DSCAM mutation impairs motor control. We investigated the motor and locomotor functions of DSCAM2J mutant mice through a combination of anatomical, kinematic, force, and electromyographic recordings. With respect to wild-type mice, DSCAM2J mice displayed a longer swing phase with a limb hyperflexion at the expense of a shorter stance phase during locomotion. Furthermore, electromyographic activity in the flexor and extensor muscles was increased and coactivated over 20% of the step cycle over a wide range of walking speeds. In contrast to wild-type mice, which used lateral walk and trot at walking speed, DSCAM2J mice used preferentially less coordinated gaits, such as out-of-phase walk and pace. The neuromuscular junction and the contractile properties of muscles, as well as their muscle spindles, were normal, and no signs of motor rigidity or spasticity were observed during passive limb movements. Our study demonstrates that the DSCAM mutation induces dystonic hypertonia and a disruption of locomotor gaits.

Sensory information from one leg has been known to elicit reflex responses in the contralateral leg, known as “crossed reflexes,” and these have been investigated extensively in cats and humans. Furthermore, experiments with mice have shown commissural pathways in detail by using in vitro and in vivo physiological approaches combined with genetics. However, the relationship between these commissural pathways discovered in mice and crossed reflex pathways described in cats and humans is not known. In this study, we analyzed the crossed reflex in mice by using in vivo electromyographic recording techniques combined with peripheral nerve stimulation protocols to provide a detailed description of the crossed reflex pathways. We show that excitatory crossed reflexes are mediated by both proprioceptive and cutaneous afferent activation. In addition, we provide evidence for a short-latency inhibitory crossed reflex pathway likely mediated by cutaneous feedback. Furthermore, the short-latency crossed inhibition is downregulated in the knee extensor muscle and the ankle flexor muscle during locomotion. In conclusion, this article provides an analysis of excitatory and inhibitory crossed reflex pathways during resting and locomoting mice in vivo. The data presented in this article pave the way for future research aimed at understanding crossed reflexes using genetics in mice.NEW & NOTEWORTHY We describe for the first time excitatory and inhibitory crossed reflex pathways in mouse spinal cord in vivo and show that the inhibitory pathways are modulated during walking. This is a first step toward an understanding of crossed reflexes and their function during walking using in vivo recording techniques combined with mouse genetics.

While it is well known that netrin-1 and its receptors UNC5 and UNC40 family members are involved in the normal establishment of the motor cortex and its corticospinal tract, less is known about its other receptor Down syndrome cell adherence molecule (DSCAM). DSCAM is expressed in the developing motor cortex, regulates axonal outgrowth of cortical neurons, and its mutation impairs the dendritic arborization of cortical neurons, thus suggesting that it might be involved in the normal development and functioning of the motor cortex. In comparison to WT littermates, DSCAM2J mutant mice slipped and misplaced their paw while walking on the rungs of a horizontal ladder, and exhibited more difficulties in stepping over an obstacle while walking at slow speed. Anterograde tracing showed a normal pyramidal decussation and corticospinal projection, but a more dorsal distribution of their axonal terminals in the spinal gray matter. Intracortical microstimulations showed a reduced corticospinal and intracortical efficacy, whereas stimulations of the pyramidal tract revealed a normal spinal efficacy and excitability of corticospinal tract axons, thus arguing for a dysfunctional cortical development. Our study reveals impairment of the network dynamics within the motor cortex, reducing corticospinal drive and impairing voluntary locomotor functions upon DSCAM2J mutation.

Differential UV spectroscopy, defined as the difference in UV absorbance spectra before and after chlorination, has shown great potential to predict disinfection by-product (DBP) concentrations at laboratory scale. However, so far, no results have been reported on the full scale application of differential UV spectroscopy in drinking water treatment facilities. The objectives of this study are to determine if relationships can be developed between differential UV absorbance and DBP concentrations, for both regulated and unregulated DBPs, in a full-scale facility and to determine if these relationships vary throughout the year with variations in raw water quality and treatment conditions. The results show that linear and power relationships between differential UV absorbance and DBP concentrations can be developed (0.62 ≤ R 2 ≤ 0.99), although differences between relationships obtained in lab- and full-scale conditions need further investigation. Finally, the relationships obtained are different from one sampling campaign to another, which raises the question of whether it is possible to determine relationships that are stable enough to be used as adequate feedback on DBP concentrations.

Locomotion is controlled by spinal circuits that generate rhythm and coordinate left-right and flexor-extensor motoneuronal activities. The outputs of motoneurons and spinal interneuronal circuits are shaped by sensory feedback, relaying peripheral signals that are critical to the locomotor and postural control. Several studies in invertebrates and vertebrates have argued that the Down syndrome cell adhesion molecule (DSCAM) would play an important role in the normal development of neural circuits through cell spacing and targeting, axonal and dendritic branching, and synapse establishment and maintenance. Although there is evidence that DSCAM is important for the normal development of neural circuits, little is known about its functional contribution to spinal motor circuits. We show here that adult DSCAM2Jmutant mice, lacking DSCAM, exhibit a higher variability in their locomotor pattern and rhythm during treadmill locomotion. Retrograde tracing studies in neonatal isolated spinal cords show an increased number of spinal commissural interneurons, which likely contributes to reducing the left-right alternation and to increasing the flexor/swing duration during neonatal and adult locomotion. Moreover, our results argue that, by reducing the peripheral excitatory drive onto spinal motoneurons, the DSCAM mutation reduces or abolishes spinal reflexes in both neonatal isolated spinal cords and adult mice, thus likely impairing sensorimotor control. Collectively, our functional, electrophysiological, and anatomical studies suggest that the mammalian DSCAM protein is involved in the normal development of spinal locomotor and sensorimotor circuits.