Alteration of body representation in typical and atypical motor development.

Developmental coordination disorder (DCD) impacts the quality of life and ability to perform coordinated actions in 5% of school-aged children. The quality of body representations of individuals with DCD has been questioned, but never assessed. We hypothesize that children with DCD have imprecise body representations in the sensory and motor domains. Twenty neurotypical children, seventeen children with DCD (8-12 years old) and twenty neurotypical adults (25-45 years old) performed both sensory and motor body representation tasks: a limb identification and a limb movement task. We observed lower accuracy in the sensory task but not in the motor task. In both tasks, we observe a larger amplitude of errors, or synkinesis, in children with DCD than in neurotypical children. In neurotypical children, accuracy was lower than in neurotypical adults in the motor and sensory task, and the amplitude of sensory errors and synkinesis was higher than in neurotypical adults. Using a linear regression model, we showed that sensory accuracy is a good predictor of synkinesis production, and that synkinesis production is a good predictor of sensory accuracy, as can be expected by the perception-action loop. Results support the hypothesis of an imprecision of body representation in DCD. We suggest that this imprecision arises from noise in the body representation used at the level of internal models of action. Future studies may assess whether slower plasticity of body representations, initial imprecision, or both may account for this observation. At the clinical level, prevention strategies targeting body representation in early childhood are strategically important to limit such impairments. RESEARCH HIGHLIGHTS: Body representation is impaired in children with DCD and has a significant cost in terms of the accuracy of sensory identification of body parts and associated movements. Inaccuracies in the body representation measured in perception and in action (error amplitude and synkinesis) are related in both NT children and adults. In typical development, we provide evidence of a strong link between body schema and body image.

The AMPK-related kinase NUAK1 controls cortical axons branching by locally modulating mitochondrial metabolic functions.

The cellular mechanisms underlying axonal morphogenesis are essential to the formation of functional neuronal networks. We previously identified the autism-linked kinase NUAK1 as a central regulator of axon branching through the control of mitochondria trafficking. However, (1) the relationship between mitochondrial position, function and axon branching and (2) the downstream effectors whereby NUAK1 regulates axon branching remain unknown. Here, we report that mitochondria recruitment to synaptic boutons supports collateral branches stabilization rather than formation in mouse cortical neurons. NUAK1 deficiency significantly impairs mitochondrial metabolism and axonal ATP concentration, and upregulation of mitochondrial function is sufficient to rescue axonal branching in NUAK1 null neurons in vitro and in vivo. Finally, we found that NUAK1 regulates axon branching through the mitochondria-targeted microprotein BRAWNIN. Our results demonstrate that NUAK1 exerts a dual function during axon branching through its ability to control mitochondrial distribution and metabolic activity.

Effects of sex and estrous cycle on sleep and cataplexy in narcoleptic mice.

Narcolepsy type 1 (NT1) is a rare neurology disorder caused by the loss of orexin/hypocretin neurons. NT1 is characterized by excessive daytime sleepiness, sleep and wake fragmentation, and cataplexy. These symptoms have been equally described in both women and men, although influences of gender and hormonal cycles have been poorly studied. Unfortunately, most studies with NT1 preclinical mouse models, use only male mice to limit potential variations due to the hormonal cycle. Therefore, whether gender and/or hormonal cycles impact the expression of narcoleptic symptoms remains to be determined. To address this question, we analyzed vigilance states and cataplexy in 20 female and 17 male adult orexin knock-out narcoleptic mice, with half of the females being recorded over multiple days. Mice had access to chocolate to encourage the occurrence of cataplectic episodes. A vaginal smear was performed daily in female mice to establish the state of the estrous cycle (EC) of the previous recorded night. We found that vigilance states were more fragmented in males than females, and that females had less paradoxical sleep (p = 0.0315) but more cataplexy (p = 0.0375). Interestingly, sleep and wake features were unchanged across the female EC, but the total amount of cataplexy was doubled during estrus compared to other stages of the cycle (p = 0.001), due to a large increase in the number of cataplexy episodes (p = 0.0002). Altogether these data highlight sex differences in the expression of narcolepsy symptoms in orexin knock-out mice. Notably, cataplexy occurrence was greatly influenced by estrous cycle. Whether it is due to hormonal changes would need to be further explored.