Generation and selection of motor behaviors neural circuits and endocannabinoid modulation

The generation of basic motor behavior relies on the activation of spinal neuronal networks called central pattern generators (CPGs). Descending drive from higher brain areas activates the spinal CPG to generate motor behavior. In the face of changes in the environment, animals make constant motor behavioral selection. Both the generation and selection of motor behavior are performed by activating hard-wired neural circuits, whose activity is further refined by neuromodulation. In this thesis, we use the spinal locomotor networks in lamprey and zebrafish to explore the neural mechanisms underlying the generation and selection of motor behaviors. Firstly, in lamprey spinal locomotor circuits, we show that the release of endocannabinoids increases the excitability of the spinal locomotor network by depressing inhibitory synaptic transmission and potentiating excitatory synaptic transmission. Secondly, we show that the behavioral selection between escape and swimming in zebrafish is mediated by a hard-wired circuit. This circuit is supplemented with endocannabinoid modulation that promotes escape and suppresses swimming. Thirdly, we uncover a novel modular organization of the spinal locomotor circuit. We demonstrate a selective pattern of connectivity between excitatory V2a interneurons and motoneurons segregating them into slow, intermediate and fast sub-circuit modules. Fourthly, we show the existence of electrical coupling between motoneurons and excitatory V2a interneurons, which extends motoneurons influence onto premotor V2a interneurons. This enables motoneurons to become embedded in the spinal circuits generating the locomotor rhythm. Overall this thesis provides insight into the mechanism of generation and selection of motor behaviors

Separate Microcircuit Modules of Distinct V2a Interneurons and Motoneurons Control the Speed of Locomotion

SummarySpinal circuits generate locomotion with variable speed as circumstances demand. These circuits have been assumed to convey equal and uniform excitation to all motoneurons whose input resistance dictates their activation sequence. However, the precise connectivity pattern between excitatory premotor circuits and the different motoneuron types has remained unclear. Here, we generate a connectivity map in adult zebrafish between the V2a excitatory interneurons and slow, intermediate, and fast motoneurons. We show that the locomotor network does not consist of a uniform circuit as previously assumed. Instead, it can be deconstructed into three separate microcircuit modules with distinct V2a interneuron subclasses driving slow, intermediate, or fast motoneurons. This modular design enables the increase of locomotor speed by sequentially adding microcircuit layers from slow to intermediate and fast. Thus, this principle of organization of vertebrate spinal circuits represents an intrinsic mechanism to increase the locomotor speed by incrementally engaging different motor units

The Asian arowana (<i>Scleropages formosus</i>) genome provides new insights into the evolution of an early lineage of teleosts

The Asian arowana (Scleropages formosus), one of the world’s most expensive cultivated ornamental fishes, is an endangered species. It represents an ancient lineage of teleosts: the Osteoglossomorpha. Here, we provide a high-quality chromosome-level reference genome of a female golden-variety arowana using a combination of deep shotgun sequencing and high-resolution linkage mapping. In addition, we have also generated two draft genome assemblies for the red and green varieties. Phylogenomic analysis supports a sister group relationship between Osteoglossomorpha (bonytongues) and Elopomorpha (eels and relatives), with the two clades together forming a sister group of Clupeocephala which includes all the remaining teleosts. The arowana genome retains the full complement of eight Hox clusters unlike the African butterfly fish (Pantodon buchholzi), another bonytongue fish, which possess only five Hox clusters. Differential gene expression among three varieties provides insights into the genetic basis of colour variation. A potential heterogametic sex chromosome is identified in the female arowana karyotype, suggesting that the sex is determined by a ZW/ZZ sex chromosomal system. The high-quality reference genome of the golden arowana and the draft assemblies of the red and green varieties are valuable resources for understanding the biology, adaptation and behaviour of Asian arowanas

The Asian Arowana (Scleropages formosus) Genome Provides New Insights into the Evolution of an Early Lineage of Teleosts

The Asian arowana (Scleropages formosus), one of the world’s most expensive cultivated ornamental fishes, is an endangered species. It represents an ancient lineage of teleosts: the Osteoglossomorpha. Here, we provide a high-quality chromosome-level reference genome of a female golden-variety arowana using a combination of deep shotgun sequencing and high-resolution linkage mapping. In addition, we have also generated two draft genome assemblies for the red and green varieties. Phylogenomic analysis supports a sister group relationship between Osteoglossomorpha (bonytongues) and Elopomorpha (eels and relatives), with the two clades together forming a sister group of Clupeocephala which includes all the remaining teleosts. The arowana genome retains the full complement of eight Hox clusters unlike the African butterfly fish (Pantodon buchholzi), another bonytongue fish, which possess only five Hox clusters. Differential gene expression among three varieties provides insights into the genetic basis of colour variation. A potential heterogametic sex chromosome is identified in the female arowana karyotype, suggesting that the sex is determined by a ZW/ZZ sex chromosomal system. The high-quality reference genome of the golden arowana and the draft assemblies of the red and green varieties are valuable resources for understanding the biology, adaptation and behaviour of Asian arowanas

Transient mTOR Inhibition Facilitates Continuous Growth of Liver Tumors by Modulating the Maintenance of CD133+ Cell Populations

The mammalian target of the rapamycin (mTOR) pathway, which drives cell proliferation, is frequently hyperactivated in a variety of malignancies. Therefore, the inhibition of the mTOR pathway has been considered as an appropriate approach for cancer therapy. In this study, we examined the roles of mTOR in the maintenance and differentiation of cancer stem-like cells (CSCs), the conversion of conventional cancer cells to CSCs and continuous tumor growth in vivo. In H-Ras-transformed mouse liver tumor cells, we found that pharmacological inhibition of mTOR with rapamycin greatly increased not only the CD133+ populations both in vitro and in vivo but also the expression of stem cell-like genes. Enhancing mTOR activity by over-expressing Rheb significantly decreased CD133 expression, whereas knockdown of the mTOR yielded an opposite effect. In addition, mTOR inhibition severely blocked the differentiation of CD133+ to CD133- liver tumor cells. Strikingly, single-cell culture experiments revealed that CD133- liver tumor cells were capable of converting to CD133+ cells and the inhibition of mTOR signaling substantially promoted this conversion. In serial implantation of tumor xenografts in nude BALB/c mice, the residual tumor cells that were exposed to rapamycin in vivo displayed higher CD133 expression and had increased secondary tumorigenicity compared with the control group. Moreover, rapamycin treatment also enhanced the level of stem cell-associated genes and CD133 expression in certain human liver tumor cell lines, such as Huh7, PLC/PRC/7 and Hep3B. The mTOR pathway is significantly involved in the generation and the differentiation of tumorigenic liver CSCs. These results may be valuable for the design of more rational strategies to control clinical malignant HCC using mTOR inhibitors

Role of Human-Mediated Dispersal in the Spread of the Pinewood Nematode in China

Background: Intensification of world trade is responsible for an increase in the number of alien species introductions. Human-mediated dispersal promotes not only introductions but also expansion of the species distribution via long-distance dispersal. Thus, understanding the role of anthropogenic pathways in the spread of invading species has become one of the most important challenges nowadays. Methodology/Principal Findings: We analysed the invasion pattern of the pinewood nematode in China based on invasion data from 1982 to 2005 and monitoring data on 7 locations over 15 years. Short distance spread mediated by long-horned beetles was estimated at 7.5 km per year. Infested sites located further away represented more than 90% of observations and the mean long distance spread was estimated at 111–339 km. Railways, river ports, and lakes had significant effects on the spread pattern. Human population density levels explained 87% of the variation in the invasion probability (P,0.05).Since 2001, the number of new records of the nematode was multiplied by a factor of 5 and the spread distance by a factor of 2. We combined a diffusion model to describe the short distance spread with a stochastic,individual based model to describe the long distance jumps. This combined model generated an error of only 13% when used to predict the presence of the nematode. Under two climate scenarios (stable climate or moderate warming), projections of the invasion probability suggest that this pest could expand its distribution 40–55% by 2025. Conclusions/Significance: This study provides evidence that human-induced dispersal plays a fundamental role in the spread of the pinewood nematode, and appropriate control measures should be taken to stop or slow its expansion. This model can be applied to Europe, where the nematode had been introduced later, and is currently expanding its distribution. Similar models could also be derived for other species that could be accidentally transported by humans

Recycling cellulase from enzymatic hydrolyzate of acid treated wheat straw by electroultrafiltration

This work explores the feasibility of recycling cellulase by electroultrafiltration (EUF), an ultrafiltration process enhanced by an electric field, to reduce the cost of enzymatic transformation of cellulose. The effect of electric field under different operating conditions (buffer concentration, acid treated wheat straw concentration, current and temperature) on flux during EUF was examined. The results showed that EUF was effective to reduce concentration polarization (CP) and enhance filtration flux in recycling cellulase. The flux improvement by the electric field could be strengthened at low buffer concentration (5 mM) and relatively low temperature (room temperature) and high current (150 mA). The flux for 2% (substrate concentration, w/v) lignocellulosic hydrolyzate increased by a factor of 4.4 at 836 V/m and room temperature, compared to that without electric field. This work shows that under appropriate operating conditions EUF can efficiently recycle cellulase from lignocellulosic hydrolyzate and thus substantially reduce hydrolysis cost. (c) 2013 Elsevier Ltd. All rights reserved