Coding in healthy and diseased neurons

点击翻译按钮获取中文摘要

Our nervous system gathers information from the environment, resulting in perceptions and appropriate behaviours. There are exciting unresolved fundamental questions about how this information is acquired and processed. This proposal uses mathematics to address three such fundamental questions. 1) How do temperature sensors work? Studying how the "experts" do it may reveal fundamental organization principles for all senses. We will investigate how snakes can detect extremely small temperature changes in their environment (due e.g. to prey). They measure heat though specialized infrared cameras on their head. They can respond to changes in the thousandth of a degree range. Work in the mid 80's suggested that this sense operates near the limit allowed by the background noise, which hampers signal detection. Since then however, extremely temperature-sensitive ion channels known as TRP receptors has been discovered in thermal sensing neurons. New electrical synchronization phenomena have also been discovered in these neurons. The proposed research will establish, using neural modeling, how important synchronization and TRP receptors are to the thermal sensitivity. This adds a fundamental link in the chain from the infrared optics of the cameras to the higher brain levels that together process infrared and visual images. 2) What is the relation between nerve damage and degradation of information flow? Nerves are a collection of "wires" known as "axons" coming out of single neurons. Fast propagation of information down a nerve, in the form of electrical pulses, relies on myelin. This myelin is made up of specialized cells that wrap around the axon, except at tiny 1 micron gaps called nodes of Ranvier. The myelin modifies the electrical properties of the axon "cable" in a way that pulses quickly jump from node to node. It also insulates one axon from the other. Myelin thins out in diseases like multiple sclerosis (MS). Recently the damage from MS can be quantified at high resolution by state-of-the-art "CARS" microscopy. My colleagues at U. Laval have provided me with images at different stages of the disease in a mouse. Our work proposes to understand and predict functional deficits in these nerves from the images. This involves modeling propagation in healthy and demyelinated single axons and axon bundles. 3) How are brain rhythms altered by stimuli? Debates rage over how rhythms are generated and what they mean. Certain brain rhythms are thought to be important for our ability to pay attention to a stimulus. Our work proposes a simple novel mechanism that can be tested in weakly electric fish brains. Paradoxically, we predict that the rhythm arises in a cell that receives a random signal plus a delayed version of that signal (such "feedforward" circuitry abounds). This will be analyzed in detail using a theory we have recently developed for the activity of cells in networks. This theory will also be expanded to explain how brain rhythms can align themselves to stimulation, a phenomenon missing in certain diseases. The work is theoretical and computational. We formulate predictive mathematical models that are simple enough to explain neural phenomena with a minimal number of biological ingredients. The work will make careful use of existing biological data, and benefit from collaborations with experimentalists. The modeling also serves the purpose of making predictions about function - via theoretical analyses or in silico experiments - which can be tested in new experiments. This research will deepen our knowledge of brain circuit function. It may also lead to novel technologies (e.g. neural prosthetics) based on newly found principles, including technologies to repair faulty circuits or to sense heat.