Craig Ferris, Ph.D. - US grants

Vasopressin is a neuropeptide that functions as a chemical messenger in the brain. It has been shown to be involved in regulating a number of behaviors, including aggression, reproduction, communication and learning and memory. Dr. Ferris has focused his efforts on the relationship between vasopressin and communicative behaviors. He has identified the neuroanatomical sites where vasopressin acts to mediate the behavior. Thus, Dr. Ferris has developed a excellent model for studying the neural circuitry of a defined behavior. Recognizing that this neuropeptide system goes through progressive changes during development, Dr. Ferris will now correlate the ontogeny of vasopressin cell bodies and vasopressin receptors with the ontogeny of the communicative and aggressive behaviors. In addition, he will examine the interaction between glucocorticoids, a family of steroid hormones secreted by the adrenal under stressful conditions, and the vasopressin system in the brain. These studies will determine whether stress during early life can have permanent effects on the brain which can alter behavior in adulthood.

Rivera 9525983 The capacity to store new information in memory is one that changes dramatically over the life span. However, little is known about the age-related changes in the brain that underlie these changes. With this award, Dr. Rivera will begin setting up a research laboratory to investigate which genes are turned on or off at different ages that may affect learning and memory. This work will provide crucial baseline information on the learning process, how it is constrained by age, and what some causes for learning dysfunction may be. ***

9550467 Zhang We propose to further conduct our research in the area of high performance parallel/distributed and computing. We will concentrate on three important problem areas: 1) investigating performance and computation problems in parallel and distributed architecture and system design; 2) developing parallel numerical methods and software for solving large real-world problems; and 3) building software tool and environment for parallel and distributed computing and performance evaluation. Our underlying goal of this research is to understand the comparative advantages and disadvantages of various types of multiprocessing hardware and software environments, and to discover new methods that efficiently solve different types of application problems on parallel and attract more minority graduate students to participate in high- performance computing research supported by our established and growing expertise in the proposed research areas. The proposed projects are major research activities in the newly established High-Performance Computing and Software Laboratory at the University of Texas at San Antonio, which has been funded by NSF, the U.S. Air Force and industries. ***

These studies will utilize functional magnetic resonance imaging (fMRI) to
examine the changes in brain activity that accompany adaptation to stress.
There is little known about the changes in brain activity associated with
adaptation to acute stress even though the neurochemical and hormonal
adaptations to stress are well known. Two closely related species, the
cotton-top tamarin and the common marmoset which have many biological and
behavioral similarities but have very distinct temperaments will be studied.
The marmoset is calmer and less anxious while the tamarin is extremely
excitable and prone to stress-related diseases like colitis and colon
cancer. Male marmosets and tamarins will be fitted into a custom designed
head and body restrainer and imaged while fully conscious inside the MRI
device for one hour each day over several consecutive days. Their brain
activity as measured by small magnetic shifts associated with changes in
blood flow to areas of increased neuronal activity will be compared and
correlated with saliva concentration of a stress hormones as they adapt to
the stress of repeated immobilization.

These studies will provide a global perspective on the neural networks in
the brain which are involved in the adaptation to repeated acute stress in
non-human primates with different temperaments. With the advent of
noninvasive fMRI in awake animals, it is now possible to follow the same
animal over several stressful events and map the global changes in brain
activity accompanying adaptation.

DESCRIPTION (provided by applicant): Adolescent use of MDMA ("Ecstasy") is a significant health problem in the United States. Human clinical studies suggest that chronic MDMA use leads to cognitive deficits and mood alterations that may be indicative of neurotoxicity. However, due to the limitations inherent in such studies, an appropriate animal model is needed to determine the neurobehavioral effects of repeated MDMA exposure during the adolescent period of development. Technology and methods have been developed for following global changes in brain neurobiology in monkeys using ultra-high field magnetic resonance imaging. Since MRI is a noninvasive technique it is possible to do prospective studies to follow developmental changes in brain structure, function and chemistry in the same subjects over the course of their lives. To this end, studies will be done on twin, adolescent marmoset monkeys, raised in their natural family environments. One twin will be exposed to oral MDMA at an intermittent schedule mirroring teenage use. The other twin will serve as a control. Animals will be periodically imaged from adolescence into adulthood to evaluate developmental changes in neurobiology. These imaging sessions will be coordinated with a series of behavioral and cognitive tests to evaluate changes in psychosocial development, learning and memory. Pharmacologic challenges and neurochemical studies on serotonergic and dopaminergic neurotransmission will be used to assess drug-induced neurotoxicity. The goal of this work is to better understand the risks of adolescent MDMA exposure on brain function, psychosocial and cognitive development.

Imaging Core The imaging capabilities at the Center for Translational Neuroimaging at Northeastern University offer unique capabilities for the visualization of nanopreparations in vivo. The center currently houses a high-resolution microSPECT/CT (NanoSPECT/CT, Bioscan, Inc.) and a 7T MR system (BioSpec, Bruker Biospin, Inc.) with a microPET to be installed in Q4 of this year. With extensive experience in onco-based imaging protocols, the imaging core enables the assessment of kinetics and dynamics of radio-labeled nanopreparations via SPECT and PET as well as nanopreparations for contrast enhanced MR studies. Multi-modal data acquisition support projects in drug development, intervention monitoring, disease diagnosis and tracking, and functional imaging. In addition to instrumentation and protocol development, the core offers a library of analysis functions for longitudinal studies of animal models of disease. Such functionality focuses on the tracking of nanopreparations via standard in vivo and ex vivo biodistribution analysis as well as novel sub-organ and sub-tumor metrics of distribution. The core hosts data and analysis results on a web-based data storage and analysis center dedicated to pre-clinical longitudinal imaging studies. Faculty and collaborating researchers have real-time access to data via the web-based repository along with remote scheduling and study-planning capabilities.

The general goals of this study are to use neuroimaging methods to measure possible changes during development and in adulthood as a function of differential birth interventions. The neuroimaging studies proposed in Project II will examine different potential mechanisms and behavioral outcomes following exposure to synthetic oxytocin (sOT) or blocking the OT receptor with an oxytocin antagonist (OTA) during birth in prairie voles. The prairie vole has been chosen as the animal model because it has a human-like autonomic nervous system, a social system characterized by high levels of sociality, long lasting pair bonds, high levels of paternal care and high levels of endogenous OT (eOT) - in the range of those measured in humans. (For details of the model see Overview and Project I). The following specific aims and questions will be addressed. Does exposure to synthetic OT (or alternatively blocking the OT receptor) at birth alter functional connectivity? Functional magnetic innaging in awake voles will be combined with independent component analysis to identify differences in resting state networks in control and experimental groups. Do manipulations including exposure to sOT or OTA at birth alter white matter tracts and fiber microstructure? Diffusion tensor imaging (DTI) and quantitative anisotropy will be used to identify areas of the brain showing changes in white matter fiber tracts and fiber microstructure between control and experimental groups. Does exposure to synthetic OT or an OT antagonist at birth affect brain activity related to perception, cognition and emotion? Imaging in awake voles will be used to identify differences in integrated neural networks functioning in: a) motivation/reward, b) anxiety/fear, and c) social recognition, as a function of birth-related interventions. These studies will be conducted and analyzed in the context of behavior, endocrine, autonomic and epigenetic measures taken in the Projects I and III.