Miles Orchinik, Ph.D. - US grants

Glucocorticoids, such as corticosterone (CORT), are an important group of steroid hormones that modulate cellular and behavioral responses to stress. Their action can involve genomic mechanisms in the cell nucleus, and also much faster non-genomic actions involving receptors on the cell membrane. The cellular mechanisms mediating responses to acute, as distinct from chronic, stress are still not well understood. Recent evidence suggests that CORT interactions with behaviorally important peptide hormones, in particular arginine vasotocin (AVT), are critical during acute stress. This project examines how CORT and AVT interact within brain cells in response to acute stress, using the salamander as a novel and accessible system to combine biochemistry with behavior. The interactions of the hormones in triggering intracellular biochemical signaling pathways will be tested in specific contexts, in terms of behavior and neuroendocrine state. Results will be important for understanding fundamental cellular mechanisms of stress hormone action in vertebrates.
The impact will extend beyond neuroendocrinology to endocrinology and stress-related behavior, as well as cell biology related to signaling. Valuable training of students at several levels in this productive laboratory also will continue to include students with handicaps and those from underrepresented groups.

This symposium on contemporary approaches to endocrine signaling is part of the annual meeting for the Society for Integrative & Comparative Biology (SICB). It addresses technical innovations that are now being applied to unconventional model organisms. Participants in this program possess expertise in neuroendocrinolgy, endocrinology, animal behavior, and developmental biology. The symposium will engage both senior and junior ranked scientists and students in discussions of the application of these new techniques that have been derived from more traditional model organisms, such as laboratory rodents. Introduction of new people to the society is enhanced by the international nature of this meeting being held in Toronto, Canada. Travel funds will allow participants to attend the meeting.
The impact of this will extend to numerous fields of study, as mentioned above. In addition, the meeting will foster scientific education by training graduate and undergraduate students to participate in comparative biological research armed with a clear understanding of this sophisticated technology. A further impact will be made when these discussions are published in the journals: Integrative & Comparative Biology and General & Comparative Endocrinology.

For most of the 20th century, the adult brain was thought to lack the neural plasticity seen in young brains and, particularly, to be incapable of generating new neurons. This perspective is falling from favor, as one of the most exciting areas of biological research is the study of adult neurogenesis - the proliferation and differentiation of neuronal progenitor cells. Researchers have recently suggested that the regulation of neurogenesis in adult humans is important in the physiology or pathophysiology of many processes, including cognition, affect, and aging (to name a few). Such avenues of research are likely to become increasingly prominent in biomedical research, but the significance of naturally occurring neurogenesis in adults of any species remains unknown. While neurogenesis in adult songbird brains appears to support seasonal cycles of song learning and memory, the definitive studies remain elusive. The current studies will take advantage of the relatively simple brain of the bullfrog, Rana catesbeiana, to enhance our knowledge of this complex process. We will combine field studies, primary cell culture, and double-labeling using laser confocal microscopy to investigate the fate of cells born in adult frog brains, attempt to identify regulatory mechanisms, and address the potential significance of adult neurogenesis from the perspective of neuroendocrine cells rather than complex behaviors. Specifc aims are to: 1) Characterize the distribution and extent of cell proliferation and the fate of newly generated cells in adult bullfrog brains; 2) Investigate seasonal and sex differences in cell proliferation and/or cell survival; 3) Characterize the proliferation, differentiation and identity of ependymal progenitors in primary culture; 4) Test the hypothesis that stress hormones alter cell proliferation, differentiation or survival; 5) Test the hypotheses that two neurochemicals that may regulate neurogenesis in mammals, serotonin and brain-derived neurotrophic factor, regulate neurogenesis in amphibians; 6) Begin investigating the potential significance of adult neurogenesis by testing the hypothesis that cell proliferation in the preoptic area and hypothalamus leads to generation of cells with known neuroendocrine functions. All the preliminary data presented in this proposal have been obtained by a group of undergraduate researchers representing diverse ethnic, age and socioeconomic groups, and a major goal of these studies is to continue providing opportunities for undergraduate and graduate student research. More than an opportunity to participate in cutting edge neuroscience, research in adult neurogenesis is intrinsically interesting to scientists and the media, making it a wonderful topic for developing student's critical reasoning skills.

In the Phoenix metropolitan area, high-need schools often experience on-going vacancies in the teaching staff and a high turnover rate of qualified teachers. This project attempts to identify and support up to 60 qualified secondary science teachers who will persist in high-need environments. Using different methods of recruitment, in conjunction with a marketing plan, science students are being identified and recruited to participate in undergraduate or post-baccalaureate programs that have extensive field experiences with diverse students, strong content knowledge requirements, and on-going opportunities to build their understanding of science as inquiry instruction. While students are completing their initial certification course work, field placements are being arranged in high need settings that consist of students who are Native American, Latina/o, or African American. Upon graduation, STARR Noyce teachers participate in science-focused induction programs, which specifically support their use of science as inquiry in diverse classrooms, their development as science teachers, and their socialization into the school community.
Ultimately, the dissemination of these findings is expected to direct future recruitment endeavors in this area.

When an organism is exposed to a wide range of stressors, a neuroendocrine cascade leads to the release of stress hormones (corticosteroids) into the bloodstream. The corticosteroids produce changes in physiology and brain function that are crucial for dealing with emergencies, but persistent elevation of corticosteroids produce the well known deleterious effects of stress. All vertebrates need a rapid and robust stress response as well as an effective means of terminating this response. The brain mechanisms that terminate this response remain poorly understood. These studies investigate a novel mechanism through which stress hormones could provide negative feedback to terminate the stress response. Collaborative experiments will be conducted at Arizona State University, University of Colorado and University of South Dakota to test the hypothesis that corticosteroids block clearance of the neurotransmitter serotonin in specific brain regions during a stress response leading to negative feedback and associated changes in behavior. State-of-the-art neurochemical, brain imaging and behavioral studies will determine whether corticosteroids block serotonin transport via a newly described transporter in brain, leading to enhanced serotonin signaling and suppression of the stress response. These studies will also serve to train students (graduate, undergraduate, and high school) and post-doctoral researchers in cutting-edge neuroscience research. The research training provided by the principal investigators (PIs) is important for encouraging young students to appreciate scientific reasoning and pursue careers in science. Collectively, the PIs have sponsored over 100 undergraduate research projects from students with diverse backgrounds, and each of the PIs also has a long track record of dedication to graduate student education and research. With these studies, each PI will continue to make explicit efforts to reach out to economically disadvantaged or underrepresented groups.