PROJECT NUMBER: IOS 0958926
Understanding how nervous systems generate behavior is a central goal of neuroscience, and much about how nervous systems work is now known. However, this knowledge is insufficient to understand how behavior is produced because nervous systems drive muscles, which in turn move the effectors (typically limbs) that produce behavior. Different muscles respond differently to nervous system input, and limbs with different anatomies respond differently to given amounts of muscle activation. Since neuro-muscular systems evolve as a unified whole, nervous system properties will vary as a function of muscle and limb properties. Understanding how nervous systems generate behavior thus requires studying the muscles and limbs that nervous systems control. The proposed work will address this issue in an extremely well-understood nervous system, the nervous system that drives the movements of the lobster stomach. The lobster stomach is more similar to vertebrate limbs than to human stomachs in that it has neurally-driven muscles and bone-like effectors called ossicles. The neural output and make-up of the stomach nervous system are completely described and a great deal about the electrical properties of its neurons is known. The stomach muscles have individual and complex responses to neural input, and a quantitative, three-dimensional description of the stomach ossicles is available. All information necessary to connect nervous system make-up and output to behavior is thus available in this system. The proposed work will characterize muscle, ossicle, and joint properties in detail so as to allow later development of a computational model of the generation of behavior in this system. Due to the analogous natures of behavior generation in this and many other systems noted above, conclusions from this work should be widely applicable, including to understanding how human nervous systems generate movement. The proposed work will also provide training on both undergraduate and post-doctoral levels.
We investigated muscle properties in the lobster stomatogastric neuromuscular system and stick insect leg muscles. This work was undertaken because muscles transform nervous system activity into force and movement. Understanding how nervous systems generate behavior thus requires understanding how muscles respond to motor neuron input. We worked in the systems above because in each of them a great deal is known about the nervous system activity. A deeper understanding of their muscles, and the ability accurately to model muscle activity, would allow connecting nervous system activity and behavior. Our research developed as we obtained additional data, and thus covered somewhat different topics than those in the original proposal. We did, however, achieve many aspects of its general goal, developing quantitatively accurate understanding of muscle properties. We first investigated how muscles passively (i.e., when the muscle's motor neurons are not firing) generate force when stretched. Previous hypotheses had attributed this ability to background binding between the molecules (actin and myosin) that generate force when muscles are activated by motor neuron activity. We showed that passive forces continue to be generated even when pharmacological treatments that block all actin and myosin interactions are applied. Passive force must thus arise from other mechanisms, likely muscle titin-like giant proteins. Muscles (the tricep) are passively stretched when their antagonists (the bicep) contract, and these passive forces are behaviorally important. Understanding how these forces develop is therefore important for understanding behavior. Our data showing that these forces are not due to actin-myosin interactions should help research in this area across preparations. We next developed, in collaboration with Bueschges' lab at the University of Cologne, a quantitative muscle model of a stick insect muscle. The generally important conclusion from this work is that muscles show great variability across individual animals, with muscle model accuracy increasing some 25% when individual specific values are used for the parameters in the models as opposed to using average values. This may not seem surprising--after all, having only one size of clothing, the average size, would not work very well--but it has two important implications. First, these differences would make the muscles have different responses to the same motor neuron input. As such, this observation indicates that the nervous system of each individual must be tuned to her/his specific muscle characteristics so that the individual's nervous system can drive the muscle appropriately to produce a desired movement. Second, it means that in musculoskeletal modeling researchers must be able to measure all the characteristics that define muscles in single experiments, since they cannot measure different characteristics in multiple muscles and average these data. Muscles are defined by a very large number of parameters, and it is difficult to measure them all in single experiments. We developed protocols to overcome these difficulties and demonstrated how to utilize them in a real system. Model building is important both for understanding how neuro-muscular systems work and for applying biological principles of motor control to robotics, and our work should help in both these goals. A third area of research we have performed is on the responses of stomatogastric muscles to temperature changes. This work was undertaken because 1) individual lobsters experience a wide range of temperatures as they move about the ocean, 2) much prior work has shown that muscle responses vary greatly with temperature (one of the advantages, presumably, of thermoregulation in mammals and birds), and 3) Marder and her co-workers had shown that certain aspects of the nervous activity driving the muscles did not vary as temperature was varied. We showed that, alternatively, stomatogastric muscles are highly temperature sensitive, stopping contraction as they were warmed only a few degrees (well within the physiologically-observed temperature range the animals experience). This seemed odd, since in vivo the animals continued to digest food (what the stomatogastric system does) even at warm temperatures. We showed that a likely explanation for this apparent discrepancy is that a modulatory substance, dopamine, that is known to be present in lobsters, counteracts the effects of temperature. This work thus suggested that modulation may in some cases not function to change the activity of neuromuscular systems, but instead to maintain it in the face of changes in internal state (in this case, temperature). The final area of our research is on how to model the temporal properties of muscle passive responses. These show a type of dynamics called power law dynamics, which are somewhat difficult to build differential equation based model of using standard muscle model components. We have found a way to do so which involves functions called hypergeometric functions. This work is particularly exciting to us because the use of this alternative approach may also have relevance to explaining the dynamics of active muscle contractions, which may lead to a unified explanation of what had heretofore been considered mechanistically separate phenomena.
