Antonio A. Nunez - US grants

Considerable evidence indicates that the 24 hr. fluctuations observed in behavioral, physiological and cognitive functions depend upon endogenous rhythmic mechanisms. In mammals, the generation of these 24 hr. or circadian rhythms is controlled by neural systems. Previous work indicates that the mammalian suprachiasmatic nucleus (SCN) is a very important component of the neural mechanism responsible for circadian rhythms. Therefore, a better understanding of the pathways connecting the SCN to the rest of the brain should increase our knowledge about the circadian regulation of behavior. The objective of the proposed research is to investigate the functional anatomy. The objective of the proposed research is to investigate the functional anatomy of the efferent connections of the SCN. To achieve this goal, neuroanatomical studies using anterograde and retrograde tract-tracing methods will be used to determine the connections of the SCN. In addition, mutant strains of rats and hamsters will be studied to determine if neuroanatomical anomalies in the SCN are correlated with deficits in the expression of circadian rhythms in behavior. Behavioral rhythms including the sleep cycle will be monitored under constant environmental conditions. Seasonal cycles in reproduction are also regulated by the SCN and by the connections between this nucleus and other hypothalamic sites. Experiments will be conducted to establish the functional anatomy of the hypothalamic circuits involved in the regulation of seasonal cycles of reproductive and regulatory functions.

Light affects daily (circadian) and seasonal cycles in physiology and behavior. Dr. Nunez will examine the neural and endocrine systems that mediate these effects of light on these biological rhythms. The suprachiasmatic nucleus of the hypothalamus is believed to be the neural substrate for the biological clock. Therefore, Dr. Nunez will concentrate on identifying the outputs of the nucleus to determine how circadian signals reach the rest of the central nervous system. Both the circadian system and the suprachiasmatic nucleus are involved in the generation of seasonal reproductive cycles but the projection or output from this neural structure involved in seasonal cycles appears to be different than the projections responsible for daily cycles. It appears that seasonal cycles may also involve the paraventricular nucleus of the hypothalamus. Dr. Nunez will also investigate the pathways that originate in this brain structure. In addition, he will elucidate the endocrine changes that are produced by neural damage that abolishes seasonal cyclicity. Information about the anatomy and physiology of this biological clock provides the basic science for a more comprehensive understanding of certain psychiatric disorders at the extreme and fluctuations in mood and productivity in the more normal range. An additional value of knowledge of controls of photoperiodism may lie in an increased efficiency in animal husbandry.

The mammalian suprachiasmatic nucleus of the hypothalamus is the anatomical substrate for a circadian biological clock that controls many overt rhythms in physiology and behavior. The mechanism(s) responsible for the generation of circadian rhythmicity by the suprachiasmatic nucleus is (are) unknown. It is known, however, that the ability to generate action potentials is not necessary for the workings of the circadian clock. Therefore, other forms of intercellular communications must mediate circadian-rhythm generation. Dr. Nunez will examine the possibility that the interaction between neurons and glial cells of the suprachiasmatic nucleus is critical. Using electronmicroscopy, he will determine whether plasticity in glial cell morphology over the circadian cycle impacts on inter-neuronal communications and, thus, impose circadian rhythmicity on the neural outputs of the suprachiasmatic nucleus. The concept of biological timing rivals that of homeostasis as an organizing principle in contemporary biology. Understanding the basic neural mechanisms may lead to treatments that could help solve problems caused by jet lag, shift work and sleep disorders in the elderly. Indeed, in so far as circadian rhythm studies will ultimately have an impact on virtually all areas of human endeavor distributed across the seasons and phases of the day, this work may have a direct effect on the nation's scientific and engineering research, education and human resources bases.

Nunez 9514374 The brain and its cells are unique in their ability to change in response to their internal surroundings and the animal's experiences. This ability to adapt can be demonstrated at the molecular, cellular and behavioral levels. One of the most plastic cells in the brain are not even nerve cells, but are peripherally derived mast cells. The mast cells and glial elements provide an enriched environment in which the nerve cells function. However, much is unknown about the mast cells in brain especially their function and anatomy. Dr. Nunez is assessing the ability of daylength, a strong environmental cue, to alter the anatomy of brain mast cells and their central nervous system location. These investigations lay the foundation for studies on the influence of mast cells on adaptive behaviors and other neurochemical changes. These investigations will provide significant basic information about the interplay between the environment and brain function. This information will then be used to further understand the how environmental factors increase or decrease species survivability in the wild or captivity.

Michigan State University (MSU) will establish a Center for Academic and Future Faculty Excellence (CAFFE). The purpose of the Center is to coordinate and integrate existing programmatic activities to train and prepare a U. S. workforce of future faculty for academic excellence and success in the tenure streams of colleges and universities. The approach of this I3 proposal aims to coordinate the efforts of multiple offices and programs at Michigan State University to optimize the development, in graduate and undergraduate students, post-doctoral scientists and junior faculty, of skills, attitudes, values and behaviors essential for smooth transitions across critical educational stages, and for success in an academic careers. There are new and rapidly changing demands and expectations for new faculty. These demands and expectations include, among others, effective pedagogy, skills in the managing and supervision of technical personnel and support staff, grant writing, and the responsible conduct of research. The establishment of the CAFFE would be a landmark step in providing a venue for the preparation of young scholars in a fashion complementary to their disciplinary professional development and aligned with what they will face as they join the academic workforce. Our plan for the delivering of the curriculum of CAFFE is guided by the appreciation that at all stages considered here, professional development takes place in an intimate disciplinary environment. Thus our approach, in contrast to a central or universal prescription of workshops and other activities, will involve a collaboration of the leadership of CAFFE with those responsible for the mentoring and education of developing scholars. Our goal is for an integration of what CAFFE offers with individualized professional and disciplinary development plans. Our approach also acknowledges that the need for particular skills and information often arises at different stages of professional development and that many activities of CAFFE would include concurrent participation of students, post-docs and faculty; we see this feature as an opportunity to enhance the flow of information across different cohorts and as the foundation for inter-generational mentoring.

Center for Academic and Future Faculty Exchange (CAFFE) brings together NSF/EHR awards from the ADVANCE and AGEP programs, as well as other work, around the I3 integrative themes for broadening participation and critical educational junctures.

The rhythmic daily patterning of activity and rest is a fundamental feature of virtually all forms of vertebrate life, including our own, and is heavily influenced by light. Light has very different effects on day-active and night-active species, with the former responding to darkness by increasing sleep and the latter responding with a decrease. Very little is known about the brain mechanisms mediating these effects of light on rest/sleep, and essentially nothing is known about how these mechanisms differ among day-and night-active species. The research to be undertaken in this project will begin to fill this gap in our fundamental understanding of these issues suing multiple approaches. First the behavioral responses to light will be directly compared in nocturnal and diurnal rodents, then the neural mechanisms mediating those responses will be characterized. The work will determine how specific populations of cells in the brain are affected by the changes in lighting conditions that affect rest and activity, and the role that these structures play in the process will then evaluated experimentally. The project outcomes could yield fundamental new insights into processes that have a profound impact on the lives of day-active animals including humans. A better basic understanding of these issues will lead to improved strategies to help the millions of Americans with sleep problems cope with them more effectively. Strategies that could be informed by the outcomes of this project include appropriately patterned administration of light, as well as, ultimately, new, safer and more effective pharmacological treatments. The project will also engage many undergraduate and graduate students in the research enterprise in ways that will provide them an inside view of how science is done.

The Michigan AGEP Alliance for Transformation (MAA) was created in response to the NSF's Alliances for Graduate Education and the Professoriate (AGEP) program solicitation (NSF 12-554) for the AGEP-Transformation (AGEP-T) track. The AGEP-T track targets strategic alliances of institutions and organizations to develop, implement, and study innovative evidence-based models and standards for STEM graduate education, postdoctoral training, and academic STEM career preparation that eliminate or mitigate negative factors and promote positive practices for underrepresented. The Michigan AGEP Alliance for Transformation (MAA): Mentoring and Community Building to Accelerate Successful Progression into the Professoriate represents a collaboration between the University of Michigan, Michigan State University, Michigan Technological University, Wayne State University, and Western Michigan University.

The long-term vision and planned outcome of MAA is to increase the success U.S. citizens who are underrepresented minority (URM) graduate students and postdoctoral scholars in all fields of STEM through graduate study, postdoctoral training and the professoriate. This vision and outcome is being addressed by pursuing the following three overarching goals of the MAA:
1) Adapting two existing models, one for fostering multidisciplinary learning communities with diverse students and the other for improving faculty mentoring of URM graduate students and postdoctoral fellows, to the needs of the five MAA campuses;
2) Studying their effects on the academic identity and career progress of U.S. citizens who are URM graduate students and postdoctoral fellows in STEM programs; and
3) Implementing more widely on campuses those models that lead to improved academic outcomes and widespread institutional change.

The objectives for this project are:
Objective 1: Designing, adapting and implementing evidence-based mentoring initiatives, on all five campuses, that are focused on improved mentoring for U.S. URM graduate students and postdoctoral fellows in all fields of STEM.
Objective 2: Designing, adapting and implementing evidence-based initiatives to promote interdisciplinary learning communities, on all five campuses, that are focused on improved mentoring for U.S. URM STEM graduate students and postdoctoral fellows.
Objective 3: Conducting research about the ways in which improved mentoring and improved sense of community are linked to a sense of academic identity, and the ways in which academic identity is linked to important academic and career outcomes, for U.S. URM graduate students and postdoctoral fellows in all STEM fields.
Objective 4: Conducting research about the ways in which departmental and university variables moderate the relations among mentoring, community, academic identity and academic outcomes for U.S. citizens who are URM graduate students and postdoctoral fellows in all STEM disciplines.

The primary activities that contribute to the model for the alliance include:
1. Designing, adapting and implementing the University of Michigan's Mentoring Others Results in Excellence (MORE) model as a foundation for improving mentoring of U.S. URM graduate students and postdoctoral fellows in STEM. This includes training facilitators who run faculty mentoring workshops, conducting mentoring workshops, training advanced level students for intergenerational mentoring, and developing/distributing individualized mentoring agreements to faculty and STEM programs.
2. Designing, adapting and implementing the Michigan State University's interdisciplinary learning community model as a foundation for improving the sense of belonging, peer support and academic identify of U.S. URM graduate students and postdoctoral fellows in STEM. This includes training facilitators, conducting institution-specific community meetings, and holding MAA-wide community meetings for graduate students, postdoctoral fellows and faculty.

The MAA includes a social science research study that will explore the mechanisms that help explain the under-representation and attrition of URM students in STEM, as well as the contextual and individual factors that can promote academic persistence and success in those fields. The research team predicts that racial/ethnic stigma experiences in students' academic contexts lead to dis-identification from the academic discipline, which then leads to lower academic performance and completion. They also predict that contextual-level resources, such as high-quality mentoring, moderate these relationships. Examples of specific study hypotheses being tested include:
1. Students reporting more negative department diversity climates (stigma experiences) will report lower sense of belonging (affective indicator of academic identity) in their academic departments than students reporting positive diversity climates.
2. Students reporting having higher quality mentoring relationships with their faculty advisors will report more positive academic identity outcomes (higher perceived preparation, higher sense of belonging, higher curricular/professional involvement) than students reporting lower quality mentoring relationships.
3. Quality mentoring will moderate the association between stigma (e.g., reported negative department climate) and academic identity (e.g., reported sense of belonging), such that the negative association of negative department diversity climate with sense of belonging will be stronger for students reporting lower quality mentoring relative to those reporting higher quality mentoring.