Rapid behavioral responses to a threat are critical for the survival of animals subjected to high predation risk. Two methods have evolved to shorten the delay between a threatening stimulus and an escape response, both by increasing the conduction velocity of nerve impulses along nerve axons: axon gigantism and myelin sheaths around the axons. Although myelin is best known in vertebrates, it is also found in two crustacean groups. These two invertebrate groups provide opportunities to understand structure-function relationships in myelin because: 1) it is possible to compare closely-related myelinated and non-myelinated forms; 2) nerve cells can be re-identified from one individual to the next, and 3) development of myelin can be tracked in identified cells through all developmental stages. In this project, physiological and computational approaches will be used in a comparative structure-function analysis of myelin in the two crustacean groups: the malacostraca and the calanoid copepods. Myelin has evolved independently in these two groups, yet it shares many features between the two, while being distinct in structure and origin. Some crustaceans transition from completely non-myelinated to fully myelinated nervous systems during development, and thus provide a good model in which to investigate nerve impulse conduction in incompletely formed myelin. Characterizing the commonalities in structure and function for myelin in copepods vs malacostracans will provide new insights into the function and evolution of vertebrate myelin. This study will start answering the question of how and why myelin evolved.
The project will train young undergraduate scientists in interdisciplinary biology and team research, build diversity in science, technology, engineering and math; and provide public access to microscopic images for educational and data mining purposes. Postdoctoral trainees on the project will be educated in the preparation and examination of material for transmission electron microscopy, extracellular electrophysiological stimulation and recording techniques, and computational modeling of neuronal functioning.
Overview: Myelin is a fatty insulating sheath that forms around nerve fibers to increase the speed with which nerve impulses travel, thus keeping remote portions of the body in closer communication and speeding brain processes. Several debilitating diseases results for malfunctioning myelin, including multiple sclerosis, which afflicts xxxx victims in the US. Understanding the way myelin functions correctly is key to understanding the way in which such diseased conditions impact health. However, vertebrate myelin is a complex structure, and it is not easy to determine which of its many facets are important in its proper functioning. A comparative approach is a powerful way of gaining insight into basic underlying biological principles. This project has studied two "model species" that differ greatly from the evolutionary line that led to vertebrates and mammals. The study highlights similarities and differences in the way in which the same function in the animal can be achieved, and.through this, have given a better appreciation of what the important features are for assuring proper function. Intellectual merit: Our comparative study of two independently-evolved cases of myelin has led to several key findings: 1. In one of our model organisms, a planktonic crustacean copepod, the project has shown that myelin is formed by a process that differs greatly from that in vertebrates. It is formed by the nerve fibers themselves. This is an unexpected departure from previous dogma, which has found only exogenous origins from specialized "glial" cells (the "glial doctrine"). It means that cellular origin is unimportant in providing the impulse-speeding functions of myelin. 2. In both of the model organisms studied, copepods and shrimp, the project has shown that myelin is formed out of concentric rings of insulating layers surrounding a fiber. This is a marked contrast to the spiral wrapping of layers in vertebrates. This again goes against the vertebrate "doctrine" that "loose" myelin is bad myelin. However, the connection to nutrient sources (the cell nucleus and cytoplasmic organelles) needed to nourish these concentric layers has not been clearly established. This highlights the value of the vertebrate design of a spiral wrapping of layers, in which the connection to nutrient sources is more evident. 3. The modeling studies conducted showed that speeding of nerve impulses can be achieved with surprisingly little "myelin" – not even enough to be identified as such. The evolutionary ball can be started rolling with subtle, easily achieved, changes in cellular organization of the glial sheath. These changes can then be built on and can lead by degrees to quite large improvements including the onset of "saltatory" conduction in which impulses jump from node to node with much greater speed than in unmyelinated fibers. Some myelin features such as specialized structures around nodes, have less predicted effect on conduction speed than is usually assumed. This realization could shift the emphasis in looking for treatment for demyelinating diseases. 4. Copepods are among the more important links in oceanic food chains. The project has shown how myelinate copepods are more resistant to predation by fish than are those lacking myelin. It has long been wondered how the open ocean has so few distinct identifiable habitats and ecological roles for its plankton (ecological "niches"). These findings point to a previously unidentified factor in myelination, which impacts our understanding of how oceanic food webs work, helping to explain the basic ecology of the ocean. The project prodduced 14 peer-reviewed publications, fully or partially supported under this award. Broader impacts: Broader Impacts: The broader impacts of the project fall into three separate categories: 1) training of future STEM workforce; 2) exposure of scientific research and its significance to a broader audience; and 3) generating resources for the scientific community. 1) NSF funding was leveraged (in combination with course credit) to provide training for undergraduates and graduate students. Two undergraduates were mentored in an NSF REU program at the Mt. Desert Island Biological Laboratory. They also attended seminars and other scientific activities. Four undergraduate students from the University of Hawaii at Manoa were biology majors from under-represented minority groups. They learned fundamental skills in immunohistochemistry, confocal microscopy and respirometry in planktonic organisms. One student used the tools she learned to complete an honors thesis project. 2) Outreach activities focused on participating in four outreach events including Open Houses both in Maine and in Hawaii. All students participated in developing displays and they interacted with the general public, sharing their knowledge in and enthusiasm for marine biology. 3) Software tools developed as part of the project ("Podbase") have been made available through GitHub, a repository of open source software projects. Extensively used by the open-source development community, contributions to GitHub are considered an important component to resume building for software engineers. Software programs for myelin modeling are in the process of being uploaded to ModelDB at Yale University.