The brain sends signals to the sense organs to focus attention on the stimuli that are most important at any given time, depending on the animal's behavioral context or physiological state. Although this type of activity has been described in the eye and ear, it has received little attention in the nose, or olfactory organ. Research by Dr. Eisthen and her collaborators suggests that the terminal nerve, a nerve that extends between the brain and nose, releases chemicals into the olfactory organ that change its activity. Specifically, the terminal nerve contains two chemicals, gonadotropin releasing hormone (GnRH) and neuropeptide Y (NPY), that change odorant responses and excitability of olfactory neurons in the nose. The effects appear to depend on the animal's overall physiological condition: GnRH is more likely to affect olfactory receptor neurons during the breeding season, and NPY?s effects are limited to hungry animals. This is interesting, because in other parts of the brain, GnRH functions to control release of hormones involved in reproduction, whereas NPY is involved in controlling appetite and hunger. The project will involve a combination of anatomical, electrophysiological, molecular, and biochemical techniques, and are expected to reveal how specific these effects are, as well as the cellular and molecular changes that underlie these effects. The research will contribute to the training of students and researchers at Michigan State University, and involves cooperation with scientists in other parts of the United States as well as in Japan and Sweden.
Intellectual Merit Scientists used to think of the sense organs as passive devices that transform stimuli from the outside world – like light, sound, or chemicals – into electrical impulses that are then processed by the brain. Nevertheless, it is clear that activity in the sense organs is modulated, or influenced, by many factors both inside and outside the body. In the work supported by this award, we examined the roles of different factors in altering the sense of smell through modulation of activity in the olfactory epithelium. Using salamanders (axolotls, Ambystoma mexicanum) as model animals, we examined the modulatory effects of peptides that are produced by the terminal nerve, a nerve that extends from the brain to the nose in many vertebrates, including humans. We found that the effects of the peptides depend on the behavioral significance of the odorant: for example, the responses to food odorants are modulated differently than are responses to odorants from other axolotls. The effects of the peptides also differed in males and females, in animals that had eaten recently vs. those that had not, and between animals in good reproductive condition vs. those that were not in reproductive condition. We also began work that will enable us to determine what kind of changes happen in the animal’s nose when it is hungry or reproductive that cause responses to modulators to change. Remarkably, despite having been studied and bred in laboratories for 150 years, the reproductive biology of axolotls has been the subject of little investigation. Therefore, in the course of this work, we also sought to develop a set of criteria that would allow us to easily determine whether or not an axolotl is in good breeding condition. In our research, we learned that axolotls are "dissociated breeders" – that the levels of circulating hormones do not correlate with reproductive physiology or behavior. Broader Impacts The research undertaken as part of this award contributed to the training of several graduate students as well as sixteen undergraduate students from diverse backgrounds. Through their lab work, students learned to design, carry out, and interpret the results of experiments using a variety of techniques. They also attended international conferences to present their work. Two undergraduate students spent a summer at the Marine Biological Laboratory in Woods Hole, MA, where, in addition to carrying out their experiments, they were able to attend course lectures and evening seminars. Finally, the research performed under this award involved personnel exchanges – in both directions – with laboratories at the University of Tokyo and Colorado State University. Thus, the award contributed to the training of students at another university as well as in Japan. The results of the research have been presented at conferences and universities in ten countries on five continents. In addition to academic audiences, our research has contributed to educational programs delivered through MSU’s Grandparents University as well as at the Fenner Nature Center in Lansing, MI.
