The extracellular matrix modulates olfactory neurite outgrowth on ensheathing cells

Primary olfactory axons grow along a stereotypical pathway from the nasal cavity to the olfactory bulb through an extracellular matrix rich in laminin and heparan sulfate proteoglycans (HSPGs) and bounded by the expression of chondroitin sulfate proteoglycans (CSPGs). This pathway is pioneered by olfactory ensheathing cells, which provide a substrate conducive for axon growth during early development. In the present study, we examined the effect of several extracellular matrix constituents on the spreading and migration, as well as the neurite outgrowth-promoting properties, of olfactory ensheathing cells. Laminin and Matrigel enhanced the spreading and migration of olfactory ensheathing cells and increased their neurite outgrowth-promoting activity. In contrast, HSPG and CSPG had little effect on the spreading and migration of olfactory ensheathing cells and hence did not promote olfactory neurite outgrowth. In vitro olfactory axons grew preferentially on the surface of olfactory ensheathing cells rather than the underlying extracellular matrix. We propose that olfactory ensheathing cells secrete laminin and HSPGs, which together with other cofactors, stimulate these cells to migrate and adopt a neurite outgrowth-promoting phenotype. Expression of CSPGs in the surrounding mesenchyme confines the growth of ensheathing cells, as well as the axons, which grow on the surface of these cells, to a specific pathway. Thus, the ECM indirectly modulates the growth and guidance of olfactory axons during development

Development of P2 olfactory glomeruli in P2-internal ribosome entry site-tau-lacZ transgenic mice

Primary olfactory neurons project their axons to the olfactory bulb, where they terminate in discrete loci called glomeruli. All neurons expressing the same odorant receptor appear to terminate in a few glomeruli in each olfactory bulb. In the P2-IRES-tau-LacZ line of transgenic mice, LacZ is expressed in the perikarya and axons of primary olfactory neurons that express the P2 odorant receptor. In the present study, we examined the developmental appearance of P2 neurons, the topographical targeting of P2 axons, as well as the formation of P2 glomeruli in the olfactory bulb. P2 axons were first detected in the olfactory nerve fiber layer at embryonic day 14.5 (E14.5), and by E15.5 these axons terminated in a broad locus in the presumptive glomerular layer. During the next 5 embryonic days, the elongated cluster of axons developed into discrete glomerulus-like structures. In many cases, glomeruli appeared as pairs, which were initially connected by a fascicle of P2 axons. This connection was lost by postnatal day 7.5, and double glomeruli at the same locus were observed in 85% of adult animals. During the early postnatal period, there was considerable mistargeting of P2 axons. In some cases P2 axons entered inappropriate glomeruli or continued to grow past the glomerular layer into the deeper layers of the olfactory bulb. These aberrant axons were not observed in adult animals. These results indicate that olfactory axons exhibit errors while converging onto a specific glomerulus and suggest that guidance cues may be diffusely distributed at target sites in the olfactory bulb

The design of a common lunar lander

The Austin Cynthesis Corporation was formed to respond to a Request for Proposal for the design of a Common Lunar Lander (CLL) capable of carrying lightweight (less than 500 kg), unspecified payload to the moon. This Final Design Report Document includes information on the requirements for the design project; the ideas proposed as solutions to the design problem; the work which has been completed in support of the design effort; justifications, validations, and verifications of decisions made during the project; and suggestions for future work to be done in support of the project. A project schedule, including current status of the items included on the schedule, as well as cost and management summaries is also included

Neogenin and RGMa control neural tube closure and neuroepithelial morphology by regulating cell polarity

In humans, neural tube closure defects occur in 1: 1000 pregnancies. The design of new strategies for the prevention of such common defects would benefit from an improved understanding of the molecular events underlying neurulation. Neural fold elevation is a key morphological process that acts during neurulation to drive neural tube closure. However, to date, the molecular pathways underpinning neural fold elevation have not been elucidated. Here, we use morpholino knock-down technology to demonstrate that Repulsive Guidance Molecule (RGMa)-Neogenin interactions are essential for effective neural fold elevation during Xenopus neurulation and that loss of these molecules results in disrupted neural tube closure. We demonstrate that Neogenin and RGMa are required for establishing the morphology of deep layer cells in the neural plate throughout neurulation. We also show that loss of Neogenin severely disrupts the microtubule network within the deep layer cells suggesting that Neogenin-dependent microtubule organization within the deep cells is essential for radial intercalation with the overlying superficial cell layer, thereby driving neural fold elevation. In addition, we show that sustained Neogenin activity is also necessary for the establishment of the apicobasally polarized pseudostratified neuroepithelium of the neural tube. Therefore, our study identifies a novel signaling pathway essential for radial intercalation and epithelialization during neural fold elevation and neural tube morphogenesis. Copyright ©2008 Society for Neuroscienc

Going beyond just-so stories

Colloquial arguments for fish feeling pain are deeply rooted in anthropometric tendencies that confuse escape responses to noxious stimuli with evidence for consciousness. More developed arguments often rely on just-so stories of fish displaying complex behaviours as proof of consciousness. In response to commentaries on the idea that fish do not feel pain, I raise the need to go beyond just-so stories and to rigorously analyse the neural circuitry responsible for specific behaviours using new and emerging technologies in neuroscience. By deciphering the causal relationship between neural information processing and conscious behaviour, it should be possible to assess cogently the likelihood of whether a vertebrate species has the neural hardware necessary to — at least — support the feeling of pain

Phenomenal consciousness in insects? A possible way forward

Klein & Barron (2016) propose that subjective experience in humans arises in the midbrain and then argue that insects have the capacity for subjective experience because their nervous system can perform neural processing similar to that of the midbrain. This approach ultimately fails because it is built on the false premise that the midbrain is the source of the awareness of sensory stimuli. I instead propose that the capacity for subjective experience must be based on fundamental neural computations that generate the “what it feels like” experience. Two such computations associated with metarepresentations and high level representations entering working memory are discussed as possible measures of the capacity for subjective experience

Appeals for “One Million Belgian Children”: Understanding the Success of the Commission for Relief in Belgium through the Mudd Family Papers

In response to the German occupation of Belgium in World War I, future U.S. president Herbert Hoover and a handful of his colleagues in the mining engineer industry founded the Commission for Relief in Belgium (CRB). The CRB engineered one of the greatest relief movements in history partly on account of its successful public appeals; nevertheless, the success of these appeals has never been fully explained due to a remarkable dearth of scholarship on the topic. This paper seeks to fill in the gap by analyzing salient documents in the Mudd Family Papers, located in Honnold/Mudd Library’s Special Collections section. The artifacts ultimately evince that the CRB tailored its appeals to the American upper and middle classes, appropriating their respective motifs and lexicons to successfully mobilize both groups; that rumors of wartime atrocities against Belgian children augmented its appeals to the middle class; and that it issued targeted messages to its American supporters after the United States’ entry into World War I, maintaining vital public support. The findings of this paper promise to add invaluable knowledge to an exceedingly understudied historical subject