Model of the early development of thalamo-cortical connections and area patterning via signaling molecules

The mammalian cortex is divided into architectonic and functionally distinct areas. There is growing experimental evidence that their emergence and development is controlled by both epigenetic and genetic factors. The latter were recently implicated as dominating the early cortical area specification. In this paper, we present a theoretical model that explicitly considers the genetic factors and that is able to explain several sets of experiments on cortical area regulation involving transcription factors Emx2 and Pax6, and fibroblast growth factor FGF8. The model consists of the dynamics of thalamo- cortical connections modulated by signaling molecules that are regulated genetically, and by axonal competition for neocortical space. The model can make predictions and provides a basic mathematical framework for the early development of the thalamo-cortical connections and area patterning that can be further refined as more experimental facts become known.Comment: brain, model, neural development, cortical area patterning, signaling molecule

Preserving neural function under extreme scaling

Important brain functions need to be conserved throughout organisms of extremely varying sizes. Here we study the scaling properties of an essential component of computation in the brain: the single neuron. We compare morphology and signal propagation of a uniquely identifiable interneuron, the HS cell, in the blowfly (Calliphora) with its exact counterpart in the fruit fly (Drosophila) which is about four times smaller in each dimension. Anatomical features of the HS cell scale isometrically and minimise wiring costs but, by themselves, do not scale to preserve the electrotonic behaviour. However, the membrane properties are set to conserve dendritic as well as axonal delays and attenuation as well as dendritic integration of visual information. In conclusion, the electrotonic structure of a neuron, the HS cell in this case, is surprisingly stable over a wide range of morphological scales

Connecting the Retina to the Brain

The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Work in the laboratory of LE is funded by the BBSRC [BB/J00815X/1] and the R.S. Macdonald Charitable Trust. Research in the laboratory of EH is funded by grants from the Regional Government [Prometeo2012-005], the Spanish Ministry of Economy and Competitiveness [BFU2010-16563] and the European Research Council [ERC2011-StG20101109].Peer reviewedPublisher PD

Transplantation of canine olfactory ensheathing cells producing chondroitinase ABC promotes chondroitin sulphate proteoglycan digestion and axonal sprouting following spinal cord injury

Olfactory ensheathing cell (OEC) transplantation is a promising strategy for treating spinal cord injury (SCI), as has been demonstrated in experimental SCI models and naturally occurring SCI in dogs. However, the presence of chondroitin sulphate proteoglycans within the extracellular matrix of the glial scar can inhibit efficient axonal repair and limit the therapeutic potential of OECs. Here we have used lentiviral vectors to genetically modify canine OECs to continuously deliver mammalian chondroitinase ABC at the lesion site in order to degrade the inhibitory chondroitin sulphate proteoglycans in a rodent model of spinal cord injury. We demonstrate that these chondroitinase producing canine OECs survived at 4 weeks following transplantation into the spinal cord lesion and effectively digested chondroitin sulphate proteoglycans at the site of injury. There was evidence of sprouting within the corticospinal tract rostral to the lesion and an increase in the number of corticospinal axons caudal to the lesion, suggestive of axonal regeneration. Our results indicate that delivery of the chondroitinase enzyme can be achieved with the genetically modified OECs to increase axon growth following SCI. The combination of these two promising approaches is a potential strategy for promoting neural regeneration following SCI in veterinary practice and human patients

Power-law for axon diameters at branch point

BACKGROUND: Axon calibers vary widely among different animals, neuron classes, and even within the same neuron. What determines the diameter of axon branches? RESULTS: We pursue the hypothesis that the axon caliber has evolved to minimize signal propagation delays, while keeping arbor volume to a minimum. For a general cost function, we show that the optimal diameters of mother and daughter branches at a bifurcation satisfy a power law. The derivation relies on the fact that the axon conduction speed scales as a power of axon diameter. Although available data are consistent with the law, there is a large spread in the data. Future experimental tests will determine whether this spread is due to biological variability or measurement error. CONCLUSIONS: Minimization of arbor volume and signal propagation delay may have been an important factor in the evolution of the brain

Topographically specific effects of ELF-1 on retinal axon guidance in vitro and retinal axon mapping in vivo

Peer reviewedPublisher PD