Growth at Cold Temperature Increases the Number of Motor Neurons to Optimize Locomotor Function.

During vertebrate development, spinal neurons differentiate and connect to generate a system that performs sensorimotor functions critical for survival. Spontaneous Ca2+ activity regulates different aspects of spinal neuron differentiation. It is unclear whether environmental factors can modulate this Ca2+ activity in developing spinal neurons to alter their specialization and ultimately adjust sensorimotor behavior to fit the environment. Here, we show that growing Xenopus laevis embryos at cold temperatures results in an increase in the number of spinal motor neurons in larvae. This change in spinal cord development optimizes the escape response to gentle touch of animals raised in and tested at cold temperatures. The cold-sensitive channel TRPM8 increases Ca2+ spike frequency of developing ventral spinal neurons, which in turn regulates expression of the motor neuron master transcription factor HB9. TRPM8 is necessary for the increase in motor neuron number of animals raised in cold temperatures and for their enhanced sensorimotor behavior when tested at cold temperatures. These findings suggest the environment modulates neuronal differentiation to optimize the behavior of the developing organism.

Dynamic regulation of neurotransmitter specification: relevance to nervous system homeostasis.

During nervous system development the neurotransmitter identity changes and coexpression of several neurotransmitters is a rather generalized feature of developing neurons. In the mature nervous system, different physiological and pathological circumstances recreate this phenomenon. The rules of neurotransmitter respecification are multiple. Among them, the goal of assuring balanced excitability appears as an important driving force for the modifications in neurotransmitter phenotype expression. The functional consequences of these dynamic revisions in neurotransmitter identity span a varied range, from fine-tuning the developing neural circuit to modifications in addictive and locomotor behaviors. Current challenges include determining the mechanisms underlying neurotransmitter phenotype respecification and how they intersect with genetic programs of neuronal specialization. This article is part of the Special Issue entitled 'Homeostatic Synaptic Plasticity'.

Electrical activity as a developmental regulator in the formation of spinal cord circuits.

Spinal cord development is a complex process involving generation of the appropriate number of cells, acquisition of distinctive phenotypes and establishment of functional connections that enable execution of critical functions such as sensation and locomotion. Here we review the basic cellular events occurring during spinal cord development, highlighting studies that demonstrate the roles of electrical activity in this process. We conclude that the participation of different forms of electrical activity is evident from the beginning of spinal cord development and intermingles with other developmental cues and programs to implement dynamic and integrated control of spinal cord function.

Regulation of feeding behaviour and locomotor activity by takeout in Drosophila.

The hormonal regulation of feeding behaviour is well known in vertebrates, whereas it remains poorly understood in insects. Here, we report that the takeout gene is an essential component of nutritional homeostasis in Drosophila. takeout encodes a putative juvenile hormone (JH) binding protein and has been described as a link between circadian rhythm and feeding behaviour. However, the physiological role of takeout and its putative link to JH remain unknown. In this study, we show that takeout (to(1)) flies failed to adapt their food intake according to food availability and that most defects could be genetically rescued. When food is abundant, to(1) are hyperphagic, yielding to hypertrophy of the fat body. When food reappears after a starvation period, to(1) flies do not increase their food intake as much as wild-type flies. This defect in food intake regulation is partly based on the action of Takeout on taste neurons, because the sensitivity of to(1) gustatory neurons to sugars does not increase after starvation, as in wild-type neurons. This lack of regulation is also evident at the locomotor activity, which normally increases during starvation, a behaviour related to food foraging. In addition, to(1) flies lack sexual dimorphism of locomotor activity, which has previously been linked to the JH circulating level. Moreover, application of the JH analog methoprene rescues the phenotype. These results suggest that takeout plays a central role as a feeding regulator and may act by modulating the circulating JH level.

Hmgcr in the corpus allatum controls sexual dimorphism of locomotor activity and body size via the insulin pathway in Drosophila.

The insulin signaling pathway has been implicated in several physiological and developmental processes. In mammals, it controls expression of 3-Hydroxy-3-Methylglutaryl CoA Reductase (HMGCR), a key enzyme in cholesterol biosynthesis. In insects, which can not synthesize cholesterol de novo, the HMGCR is implicated in the biosynthesis of juvenile hormone (JH). However, the link between the insulin pathway and JH has not been established. In Drosophila, mutations in the insulin receptor (InR) decrease the rate of JH synthesis. It is also known that both the insulin pathway and JH play a role in the control of sexual dimorphism in locomotor activity. In studies here, to demonstrate that the insulin pathway and HMGCR are functionally linked in Drosophila, we first show that hmgcr mutation also disrupts the sexual dimorphism. Similarly to the InR, HMGCR is expressed in the corpus allatum (ca), which is the gland where JH biosynthesis occurs. Two p[hmgcr-GAL4] lines were therefore generated where RNAi was targeted specifically against the HMGCR or the InR in the ca. We found that RNAi-HMGCR blocked HMGCR expression, while the RNAi-InR blocked both InR and HMGCR expression. Each RNAi caused disruption of sexual dimorphism and produced dwarf flies at specific rearing temperatures. These results provide evidence: (i) that HMGCR expression is controlled by the InR and (ii) that InR and HMGCR specifically in the ca, are involved in the control of body size and sexual dimorphism of locomotor activity.

Disruption of insulin pathways alters trehalose level and abolishes sexual dimorphism in locomotor activity in Drosophila.

Insulin signaling pathways are implicated in several physiological processes in invertebrates, including the control of growth and life span; the latter of these has also been correlated with juvenile hormone (JH) deficiency. In turn, JH levels have been correlated with sex-specific differences in locomotor activity. Here, the involvement of the insulin signaling pathway in sex-specific differences in locomotor activity was investigated in Drosophila. Ablation of insulin-producing neurons in the adult pars-intercerebralis was found to increase trehalosemia and to abolish sexual dimorphism relevant to locomotion. Conversely, hyper-insulinemia induced by insulin injection or by over-expression of an insulin-like peptide decreases trehalosemia but does not affect locomotive behavior. Moreover, we also show that in the head of adult flies, the insulin receptor (InR) is expressed only in the fat body surrounding the brain. While both male and female InR mutants are hyper-trehalosemic, they exhibit similar patterns of locomotor activity. Our results indicate that first, insulin controls trehalosemia in adults, and second, like JH, it controls sex-specific differences in the locomotor activity of adult Drosophila in a manner independent of its effect on trehalose metabolism.

Neuroendocrine control of a sexually dimorphic behavior by a few neurons of the pars intercerebralis in Drosophila.

In Drosophila, locomotor activity is sexually dimorphic and the brain area controlling this dimorphism has been mapped. The neurons of the pars intercerebralis (PI) have been suggested to participate in such differences between males and females. However, the precise physical nature of the dimorphism, the identity of the PI neurons involved, and the nature of the neuronal signal coding the dimorphism remain unknown. In this study, we used a video-tracking paradigm to characterize further the pattern of locomotor activity in Drosophila. We show that the number of activity/inactivity periods (start/stop bouts) is also sexually dimorphic, and that it can be genetically feminized in males. Moreover, the transplantation of PI neurons from a female, or of feminized PI neurons from a donor male into a receiver wild-type male is sufficient to induce the feminization of locomotor behavior, confirming that this tiny cluster of approximately 10 neurons is directly responsible for the sexual dimorphism in locomotor activity. Finally, feeding males with fluvastatin, a juvenile hormone (JH) inhibitor, also led to start/stop feminization, and this effect is reversible by the simultaneous application of methoprene, a JH analog, suggesting the existence of a neuroendocrine control, by JH, of such behavioral dimorphism.