Stuart M. Zola - US grants

A major goal of this project is to establish an animal model of bitemporal human amnesia. The development of an experimental animal model for the study of a clinical disease entity in humans has always been one of the goals of neuroscience research. We are proposing a program of study in monkeys involving the bitemporal brain regions that have been implicated in human amnesia, and in normal human memory processes. This research program should help identify which specific brain structures are involved in human amnesia and clarify how they are involved. Specifically, the work is designed to 1) clarify further the effects on memory of separate or combined bilateral damage to the hippocampus and the amygdala in monkeys, when memory is tested with four tasks similar to those sensitive to human amnesia; 2) determine the effects of distraction on the performance of two delay-type tasks in normal and operated monkeys; 3) determine whether a newly formulated distinction, between that kind of learning which is spared in human amnesia and that which is not, can be demonstrated in monkeys with temporal lobe lesions. Performance will be compared on pattern discrimination learning and delayed retention of object discriminations; 4) determine if the effects of bitemporal lesions extend to both recognition memory (the ability to remember which of two objects is equally familiar) and association memory (the ability to remember which of two equally familiar objects was associated with reward). Equivalent tests of recognition and association memory will be given to all groups. 5) Determine if the behavioral effects of bitemporal lesions extend beyond the visual modality by administering analagous tests in the auditory mode; 6) determine if there is a discontinuity between premorbid and postmorbid memory in monkeys with bitemporal damage by operating on the normal group who have previously learned the tasks and retesting them.

A major goal of this project is to establish an animal model of bitemporal human amnesia. The development of an experimental animal model for the study of a clinical disease entity in humans has always been one of the goals of neuroscience research. We are proposing a program of study in monkeys involving the bitemporal brain regions that have been implicated in human amnesia, and in normal human memory processes. This research program should help identify which specific brain structures are involved in human amnesia and clarify how they are involved. Specifically, the work is designed to 1) clarify further the effects on memory of separate or combined bilateral damage to the hippocampus and the amygdala in monkeys, when memory is tested with four tasks similar to those sensitive to human amnesia; 2) determine the effects of distraction on the performance of two delay-type tasks in normal and operated monkeys; 3) determine whether a newly formulated distinction, between that kind of learning which is spared in human amnesia and that which is not, can be demonstrated in monkeys with temporal lobe lesions. Performance will be compared on pattern discrimination learning and delayed retention of object discriminations; 4) determine if the effects of bitemporal lesions extend to both recognition memory (the ability to remember which of two objects is equally familiar) and association memory (the ability to remember which of two equally familiar objects was associated with reward). Equivalent tests of recognition and association memory will be given to all groups. 5) Determine if the behavioral effects of bitemporal lesions extend beyond the visual modality by administering analagous tests in the auditory mode; 6) determine if there is a discontinuity between premorbid and postmorbid memory in monkeys with bitemporal damage by operating on the normal group who have previously learned the tasks and retesting them.

DESCRIPTION (provided by applicant): Despite significant scientific advances in the past decade leading to improved treatments and the prospect of a vaccine, AIDS continues to be a major medical problem world-wide, with new infections and deaths in the millions annually. Progress in AIDS research must continue if we are to be successful in containing, then eliminating, this global scourge. The availability of non-human primate models is a critical requirement to conduct the basic research and pre-clinical testing required to develop better treatments and vaccines. The NIH/NCRR supported Yerkes NPRC has played a significant role in AIDS animal model studies for some years - allocating substantial resources to this effort. AIDS related research projects continue to increase at the YNPRC funded largely by the NIH. In recent years, the Center has experienced accelerated growth in the scope of its research programs and research-support activities, as work with nonhuman primate models has become increasingly important in a number of realms. Consequently, the demand for infrastructure needed to support research vital to national health needs has increased both at Yerkes and nationally. This proposal requests funds to renovate an existing conventional primate housing facility into a BSL-2+ Primate Housing Facility suitable for holding monkeys assigned to AIDS-related research protocols. The design of the facility will follow the recommendations in the CDC-NIH Biosafety in Microbiological and Biomedical Laboratories Manual, 4th edition, May 1999. The proposed renovation will provide BSL-2+ housing for up 192 animals, an increase of 66% over current capacity. The requested improvements will provide us with critically needed additional housing dedicated for AIDS studies, which will augment both the scope and pace of our AIDS-related research.

We propose three highly interrelated studies that will utilize the cohorts of stressed and control nonhuman primates that were generated during our previous funding period of the Conte grant. Study 1 (investigator: Stuart Zola, Ph.D.) asks what are the effects of early stress on subsequent cognitive abilities, with a particular emphasis on declarative and nondeclarative memory functions. Behavioral tasks that are selectively sensitive to medial temporal damage, to striatal damage, and to frontal lobe damage, respectively will be used to assess the impact of early life stress on subsequent development of cognitive abilities, especially memory function. Study 2 (investigators: Lisa Parr Ph.D., Mar Sanchez, Ph.D.) asks what are the effects of early stress on the development of emotional behavior, with an emphasis on fear and anxiety, and changes in cerebral glucose metabolism. Study 3 (investigator: Leonard Howell, Ph.D.) asks whether early stress results in subsequent vulnerability to acquiring cocaine self-administration more rapidly than control monkeys, and whether early stress makes one more resistant to extinction compared to control monkeys. All of the studies will use structural and/or functional brain imaging to additionally clarify the relationship between behavioral changes and changes in brain, and will obtain neuroendocrine, HPA axis function, and other neurochemical assessments to clarify the relation between behavioral changes and brain chemistry as a consequence of early life stress. An additional advantage is that Study 1 and Study 2 will use the same groups of monkeys. This is both an efficient use of this very valuable resource, and it allows us to directly compare findings in two different domains of behavior, i.e., memory and emotion, in the very same animals. By necessity, an entirely separate group of monkeys will be used for Study 3. The findings from all of the studies proposed here using nonhuman primate animal models will have important theoretical implications as well as obvious clinical relevance and direct application to understanding the effects of early life stress on subsequent human cognitive and emotional development and function. In particular, this work will identify brain regions that are vulnerable to the effects of early stress. Moreover, the findings should illuminate important points about the organization of memory, emotion, and addictive-like behavior in the mammalian brain.

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This project is an interdisciplinary, inter-institutional research and education program in behavioral neuroscience. The project includes over 80 faculty from 8 Atlanta colleges and universities including 5 schools that primarily serve African-American students. The scientific program focuses on the neural basis of social behaviors using molecular, cellular, and sytematic approaches. The administrative home and several research labs for the Center are based at Yerkes. The Center funded from the NSF and the State of Georgia.

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This research project is part of an Alzheimer's Disease Research Center (ADRC) grant awarded in 2005. The major goal of this work is to determine whether sensitive behavioral tasks, together with eye-tracking technology, will reveal a profile of performance in MCI patients that is useful in predicting the onset of Alzheimer's disease. The overall plan is to test 60 MCI patients, 60 matched normal control (NC) subjects, 30 patients with Alzheimer's Disease (AD) and a group of 30 Parkinson's Disease patients without dementia (PD). All subjects have been recruited from the ADRC Clinical Core. Each subject is tested annually. We have successfully administered the preferential looking task together with eye-tracking in these subjects and are currently collecting Year 4/Year 5 data. An important contribution from this work would be the ability to diagnose sooner than is now possible in MCI patients oncoming cognitive decline, at a time when the nervous system is less compromised and, accordingly, more likely to benefit from therapeutic intervention. It is useful to note that the task we are using in our patient populations to detect early memory impairment is the same task we first developed for use in nonhuman primates for detecting damage to the hippocampus. Indeed, this task, called the Preferential Looking Task, when combined with eyetracking technology, has turned out to be one of the most sensitive tasks we now have for assessing memory dysfunction in both human and nonhuman primates.

Animal Euthanasia; Animals; Blood; Breeding; CRISP; Cercocebus; Clinical; Collection; Computer Retrieval of Information on Scientific Projects Database; Disease; Disorder; Epidemiology / Surveillance; Euthanasia, Animal; Funding; Grant; Health; Injury; Institution; Investigators; Lophocebus; Macaca; Macaque; Maintenance; Maintenances; Mangabeys; Medical Inspection; Medical Surveillance; Mercy Killing, Animal; Movement; NIH; National Institutes of Health; National Institutes of Health (U.S.); Physical Examination; Procedures; Purpose; Records; Research; Research Personnel; Research Resources; Researchers; Resources; Reticuloendothelial System, Blood; Source; Surveillance; Tuberculin Test; United States National Institutes of Health; animal care; animal colony; animal resource; body movement; disease/disorder; ppd (purified protein derivative of tuberculin)

Amygdala; Amygdaloid Body; Amygdaloid Nucleus; Amygdaloid structure; Area; Behavioral; Brain; CRISP; Computer Retrieval of Information on Scientific Projects Database; Encephalon; Encephalons; Expectancy; Funding; Goals; Grant; Institution; Investigators; Learning; Mammals, Primates; Methods and Techniques; Methods, Other; Monkeys; NIH; National Institutes of Health; National Institutes of Health (U.S.); Nervous; Nervous System, Brain; Outcome; Primates; Research; Research Personnel; Research Resources; Researchers; Resources; Rewards; Role; Source; Techniques; Training; United States National Institutes of Health; Work; amygdaloid nuclear complex; cognitive function; frontal cortex; frontal lobe; neural; preference; relating to nervous system; response; social role; visual stimulus

brain imaging /visualization /scanning

[unreadable] DESCRIPTION (provided by applicant): [unreadable] This conference grant (R13) application requests funds to partially cover the cost of planning, organizing, publicizing and hosting the 24th Annual Symposium on Nonhuman Primate Models for AIDS. The symposium will be held October 4-7, 2006, at the Omni Hotel at CNN Center in downtown Atlanta, Georgia, and will be hosted by the Yerkes National Primate Research Center, Emory University. This meeting is the premier forum for the presentation and exchange of the most recent scientific advances in AIDS research utilizing the nonhuman primate model. The latest findings in primate pathogenesis, immunology, genomics, virology, vaccines and therapeutics will be presented. It is anticipated more than 300 scientists from the United States and other countries will attend. The symposium will encompass five half-day scientific sessions and an evening poster session. The scientific sessions will be: Virology, Pathogenesis, Immunology, Vaccines and Therapeutics/Genomics. Each session will have an invited Chair, a scientific leader in the field, who will give a 30-minute state-of-the-field presentation to open the session, and a Co-Chair from the Scientific Committee, who will moderate the session and entertain questions. In addition, there will be an invited keynote speaker and a banquet speaker, who will address scientific approaches and concerns regarding the global AIDS crisis and related issues of public health. A Scientific Program Committee consisting of eight-ten members drawn from the Yerkes/Emory community and other institutions will review abstracts and assign oral or poster presentations for each of the scientific sessions. Committee members will include leaders in the field from a variety of scientific disciplines. Criteria for selection of oral presentations will include relevance of the topic as well as originality and quality of the information contained in the abstract. Those giving talks will be invited to submit their presentations in manuscript form for publication in the Journal of Medical Primatology. A poster session will include meritorious presentations that cannot be accommodated in one of the platform sessions. A local Organizing Committee will handle arrangements and logistics for the symposium. Feedback from the participants will be obtained through written questionnaires or oral comments to members of the organizing committee. This format has been successfully followed using NCRR support for the previous Annual symposium. [unreadable] [unreadable] [unreadable]

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The Yerkes nonhuman primate colony is maintained by the Division of Animal Resources, which is responsible for veterinary and animal care, environmental enrichment, animal records and provision of research support. Maintenance of such a resource requires certain animal care and use procedures that are an integral part of the support of such a colony. These include: holding the animals in captivity;maintaining breeding colonies ((including SPF macaque and mangabey colonies for AIDS research);movement and handling of the animals as required for management purposes;periodic health surveillance, which may include physical examination, tuberculin testing, radiographs, blood collections;treatment of intercurrent diseases and injuries;and occasional euthanasia of animals unresponsive to treatment or animals with untreatable clinical problems or injuries.

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Increasingly, research conducted at the Yerkes National Primate Research Center depends on high bandwidth, dependable and secure data networks. The data network improvement project provides benefit to all research conducted at Yerkes by providing a new, reliable fiber optic network within Yerkes and better connecting Yerkes to partner institutions. These improvements meet the rigorous data networking needs of medical imaging, molecular databases and tele-medicine while providing new capabilities to share large data sets with researchers collaborating on important topics such as vaccine development, brain disease, heart disease, eye disease and other human diseases. The funds in this administrative supplement are used to make key improvements to the data network at the Yerkes National Primate Research Center. The objectives of the program include three core elements: 1) improve reliability of the internal data network by adding underground fiber optic links between key buildings and installing new network switches within each building;2) provide network bandwidth improvements that will support the increasingly large data volumes being exchanged routinely between workstations, servers, scientific equipment and outside institutions and 3) establish new data network security features that will improve the ability to securely share information from systems located at the Yerkes National Primate Center with other institutions globally. Collectively, these improvements are foundational for supporting informatics, translational research and data sharing. This supplement is aligned with the goals of the American Recovery and Reinvestment Act of 2009 by providing employment to people involved in the design, installation and configuration of data network improvements. This supplement will accelerate the pace of achievements in scientific research at the Yerkes National Primate Research Center by providing significant connectivity and reliability improvements to the data network utilized each day in all research and veterinary care efforts.

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. In line with the goals of our P51 parent grant, The Yerkes NPRC has successfully developed a program using nonhuman primate models and brain imaging technologies for studying stroke and stroke intervention. The focus of this program is related directly to the component of our P51 parent grant intended to enhance research applicable to the solution of human health problems, i.e., translational research. Specifically, funds were requested to recruit a lead scientist in the areas of stroke and brain imaging research. The Yerkes Center under its P51 parent grant has developed significant infrastructure support for an emerging stroke and brain imaging program (both MRI and PET) based on research with nonhuman primates. Additionally, we have established an active research group of junior investigators at Yerkes who focus on stroke models in nonhuman primates using brain imaging. We have a number of clinicians in the School of Medicine at Emory University who are strongly engaged in our program of nonhuman primate models for stroke research. Moreover, we link collaboratively to several other imaging groups throughout Emory University. We have successfully completed the recruitment process and believe the presence of a leader in stroke/imaging will positively impact not only our research program, but also our training of researchers, students and our ability to compete for grants and awards.

DESCRIPTION (provided by applicant): The Yerkes National Primate Research Center at Emory University is one of eight national primate centers in the United States. With an average daily census of 3400 nonhuman primates (NHPs), the Center supports multidisciplinary translational research in microbiology and immunology, neuroscience, psychobiology and sensory-motor systems. The Center, adjacent to the Centers for Disease Control and Prevention, has grown to become a vital component of the NIH's National Center for Research Resources and currently supports approximately 150 NIH funded projects. However, continued growth of research programs and funding successes have outstripped the capacity of our existing infrastructure to support the basic and translational research for which the Center is so well recognized. In particular, the lack of sufficient NHP ABSL3 space for work on infectious diseases and the increased need for space-intensive facilities required for work with immunocompromised animals has significantly curtailed the Center's ability to respond to national research priorities. Accordingly, this C06 proposal requests funds for construction of a new dual function 19,800 sq ft building devoted to NHP research in two of the most rapidly growing areas of the Yerkes research portfolio that align with national health priorities - infectious disease and transplant medicine. This new facility will address major unmet needs in tuberculosis and other emerging infectious disease threats, and will further the development of immune therapies to reduce morbidity and mortality associated with bone marrow, organ, and tissue transplants. The first floor of the building will be dedicated to infectious disease research, with an ABSL3 capacity for 108 animals in 4 self-sufficient environmentally contained areas that will permit up to 4 concurrent studies, each with unique high-risk agents without danger of cross contamination. The third floor will be dedicated to the Transplant Medicine Facility, have a capacity for quarantine of 80 NHPs and housing up to 168 NHPs post transplant, will include a suite for profoundly immunocompromised animals, and a dedicated operating room for dual transplant donor/recipient surgeries. All building maintenance functions will be housed in an innovatively designed second floor interstitial space so that service and equipment maintenance functions can be performed without the need to enter either ABSL3 space or specialized space for immunocompromised animals. The air handling systems for the ABSL3 floor and the transplant floor will be entirely separated and isolated from each other to preclude the possibility of cross contamination. Construction of this dual function facility will create jobs for an extensive labor force over the next 2 plus years. Moreover, the operation of this new facility will create new positions for at least 12 skilled FTEs, including 6 research personnel, 1 dedicated building manager, 3 animal caretakers, 1 veterinary technician and 1 ABSL3-trained animal research specialist.