Center News

Roles and Responsibilities

Behavioral Management Services (BMS) is part of the WaNPRC Division of Primate Resources and is tasked with assuring the psychological well-being of the nonhuman primates housed at the Center. The overarching goal of Primate Resources is to provide an optimal environment for conducting biomedical research at the WaNPRC. In order to assure the psychological well-being of the animals housed at our center, BMS oversees the implementation of the WaNPRC Environmental Enhancement Plan.

BMS also monitors and treats any abnormal behaviors, should they arise, and trains all incoming personnel regarding the Environmental Enhancement Plan, nonhuman primate behavioral ecology and how to behave while in the vivarium to avoid causing undue stress to the animals. BMS has a dedicated trainer that utilizes positive reinforcement training techniques to encourage a variety of behaviors including voluntary cooperation with various research and veterinary procedures. Voluntary cooperation not only increases the well-being of the animals by decreasing stress that can be associated with these procedures it also increases the safety of personnel working with the animals. All species of NHPs housed at our facility live in large social groups in the wild and social contact is best way to enrich the lives of our NHPs as well avert and ameliorate any problematic behavior. Therefore, one of the most important aspects of our behavioral management program is providing a compatible social partner to all animals that are allowed to have one. BMS also monitors ongoing compatibility in social pairs.

Research Conducted by Behavior Management Services

Behavioral management programs at all National Primate Research Centers have another mission that is less well known. They are charged with contributing to the establishment of professional standards for animal care through research, publication of experimental results in peer reviewed journals. We also present on our research at scientific meetings. Research topics are expected to include evaluation of environmental enhancement strategies, behavioral monitoring and treatment strategies as well as other aspects of the behavioral management program. The BMS research program at the WaNPRC has been especially productive during the last several years during which time members of the BMS team have been authors or co-authors on eight manuscripts that are published or in press in peer-reviewed journals. They have also been authors or co-authors on 19 talks and posters presented at national and international meetings.

BMS has evaluated toys and foraging devices utilized by the WaNPRC as well as aspects of structural enrichment such as shelves and wheels in the compounds. They have also evaluated the feasibility of providing water enrichment pools to compound-housed juveniles. A significant contribution to behavioral management strategies has been the development of an innovative and effective treatment for locomotor stereotypy involving access to increased vertical space. BMS has also undertaken an assessment of WaNPRC nursery rearing strategies by evaluating behavioral outcomes for juveniles as well as adults housed at our various facilities. Both studies found that animals reared in our nursery exhibited normal behavioral repertoires. BMS has also made significant contributions to the understanding of alopecia (hair loss) which poses a significant management challenge and has received increased attention by regulatory agencies in recent years. It had been commonly thought that the two primary causes of alopecia were attributable to hair plucking and stress. Studies conducted by BMS in collaboration with the Oregon and Southwest Primate Research Centers and the University of Massachusetts Amherst have found that the majority of animals with alopecia do not hair pluck. This collaborative study also found that alopecia was associated with significantly higher levels of hair cortisol (possibly indicative of stress) at one center, but unrelated to hair cortisol at two other centers. Studies at the WaNPRC have also shown that, in general, pigtail macaques exhibit more alopecia than rhesus macaques. Studies have also shown that animals purchased from different vendors have significantly different levels of alopecia depending on their facility of origin. These differences can persist for extended periods of time (up to 10 months after entry into our facility). Thus, taken together, these studies demonstrate that the etiology of alopecia is considerably more complicated than has been commonly thought. BMS is currently investigating effects of various ameliorative therapies on alopecia as well as pharmaceutic therapies for abnormal and atypical behaviors.

Julie Worlein  |  Research Scientist  |  Behavioral Management Services

“Memory Enhancement with Modeling, Electrophysiology, and Stimulation (MEMES)”

Principal Investigator: Beth Buffalo

ABSTRACT:  The RAM Program seeks to develop new technologies for using brain stimulation to enhance human memory. The MEMES team seeks to achieve this goal via a diverse and experience group of neuroscientists, neurosurgeons and corporate partners that will perform theoretical and empirical studies designed to identify optimal stimulation parameters and methodologies for human memory enhancement. These parameters will be identified and refined via brain recordings in neurosurgical patients. These studies are designed to build towards the end goal of creating an implantable device that can be used by patients with memory disorders. The role of the University of Washington (PI: Elizabeth Buffalo, Ph.D.) in this research program is to oversee research studies regarding the neuronal representation of spatial knowledge in the nonhuman primate brain and the assessment of the ability of direct brain stimulation to enhance these representations. This work will be carried out via collaboration with clinical studies involving human patients, both here ate UW and with neurosurgeons and neurologists at multiple hospitals. The University of Washington’s work in this program consists of several components to support the MEMES research proposal. First, UW will adapt experimental paradigms that are designed to assess how the human brain represents spatial information for use in the nonhuman primate. Second, UW will perform neurophysiological recordings of both single units and network neural activity while monkeys perform tasks of spatial navigation in the presence and absence of direct brain stimulation. This will provide insight into the functional correlates of neural activity and reveal the neurophysiological effects of neuronal stimulation. Third, UW will collaborate with partner institutions in using the ensemble neural data obtained in monkeys to contrain and develop computational models of how direct brain stimulation might be used to alter a patient’s brain state to improve the efficiency of their memory encoding. Fourth, UW will develop and test a novel closed-loop real-time methodology for using brain stimulation to enhance spatial memory performance in monkeys. The overarching goal of all of these studies is to develop and test methodologies in nonhuman primates that can be directly translated into patients in the service of improving memory.

“Impact of cannabis on pathogenesis in treated HIV infection”

Principal Investigator: Nikki Klatt

ABSTRACT:  With 35 million HIV-infected individuals worldwide, containment and eventual eradication of the AIDS pandemic remains a top priority in contemporary biomedical research. While antiretroviral therapy (ART) can improve health during HIV infection, a cure is not yet available, and despite suppression of viremia with ART, these individuals still have increased morbidity and mortality compared to uninfected individuals. Indeed, HIV-infected subjects cannot discontinue ART, because residual HIV persists, and virus rebound is inevitable if ART is terminated. The HIV reservoir is complex, and at least two mechanisms drive this latent pool of infected cells, including residual low levels of virus replication in anatomical sanctuaries (such as the gastrointestinal tract), and persistent proviral HIV DNA that is integrated into the host genome in long-lived cellular reservoirs. Furthermore, HIV is closely associated with, and potentially driven by, immune activation and inflammation during HIV infection. The pathology of disease caused by HIV infection is complex and multifaceted. In addition to high levels of systemic viral replication, HIV infection results in a vicious cycle of mucosal damage, chronic inflammation and overall immunological dysfunction, which are closely associated with disease. This chronic immune activation is strongly associated with gastrointestinal (GI) mucosal damage and microbial translocation, which do not resolve completely with ART. While there is a clear positive correlation between measures of immune activation and HIV persistence in ART-suppressed individuals, whether immune activation is a cause, a consequence or both a cause and a consequence of HIV persistence is unknown. Here, we propose a provocative approach to directly evaluate whether decreasing inflammation during ART-suppressed lentiviral infection results in a decreased HIV reservoir, using an extremely novel therapeutic concept.

“Developmental Neurotoxicity of Domoic Acid in Nonhuman Primate Model”

Principal Investigator: Tom Burbacher

Domoic Acid (DA), is a naturally-occurring biotoxin that can contaminate harvestable populations of finfish and shellfish in ocean waters. Exposure to DA is associated with a constellation of clinical symptoms that can include gastrointestinal distress, confusion, transient and permanent memory loss, coma and death. Animal studies have demonstrated a strong fetal sensitivity to this environmental toxin. The toxic algal blooms that produce DA appear to be increasing in frequency and toxicity and pose a growing threat to human health and seafood safety. Very little is known about the effects of chronic, low-dose exposure to DA, a pattern of exposure that would particularly represent coastal-dwelling indigenous communities that rely on the ocean as a vital source of food and cultural identity. Given that episodes of DA contamination are becoming more frequent, a legitimate concern arises as to whether DA may negatively affect fetal development at levels of exposure that do not product overt signs of neurotoxicity or illness in pregnant women. To elucidate the maternal and developmental neurotoxicity of Domoic Acid, we propose to conduct the first study of chronic, low-level, oral DA exposure in a nonhuman primate model with outcome measures that embrace pharmacokinetics, neuropathology, stereology, neuroimaging and neurobehavioral assessment. The results of this study will provide important information on the neurotoxic consequences of DA exposure during pregnancy and the resulting effects on infant health and development.

“CRCNS: Information processing in cerebral cortex for visual-oculomotor behavior”

(CRCNS = Collaborative Research in Computational Neuroscience)

Principal Investigator: Mike Mustari

The primate visual and oculomotor system allows tracking of small visual objects and large moving visual scenes to support optimal visual acuity and visual motor behavior. We use volitional smooth pursuit (SP) eye movements and reflex-like optokinetic (OKR) eye movements to support visual function. Both classes of tracking eye movements require cerebral cortical processing of visual inputs to create initial commands for eye movements. Volitional SP and OKR behaviors offer important perspectives on neural mechanisms that produce sensory-motor behavior, perception and cognitive processing. Our studies focus on the frontal eye fields (FEF) and parietal cortex (MSTd, MSTl, MT), which have been shown to play a role in SP, OKR and perception. However, the information passed between these areas during tracking eye movements remains unknown. Our studies will address this gap in knowledge by providing the first comparative data on visual, eye movement and task related signals carried in feedforward and feedback pathways between frontal and parietal cortex. We will apply novel computational approaches for data analysis, model the functional contributions of frontal and parietal cortex to tracking eye movements, and finally test the model predictions using electrical stimulation and optogenetic techniques to reversibly perturb signaling in this cortical-cortical network. There are extensive cortical-cortical connections between brain regions but we lack specific information about the role of these connections in complex sensory-motor behavior. Our studies are organized under 3 specific aims to experimental and computational approaches that build on information theory and related statistical methods to account for how different signals(e.g., visual, eye movement) are combined and interact to support purposeful behavior. Our experimental work provides novel neurophysiological data taken from frontal and parietal cortical neurons that we identify as projecting from one brain region to another and 2) the experimental results will be directly compared to simulations developed in computational models of cortico-cortical interaction.

***Now listed under the Core Services tab at:
Instrumentation Services

Bioengineering Division Focus

The Bioengineering division has been part of the Washington National Primate Research Center since its inception. Today, our focus is on developing instruments, tools, or other technological solutions when these cannot be obtained off-the-shelf; modifying them to meet altered requirements; or simply repairing them. While the WaNPRC Neuroscience Core researchers are our primary clients, we support all the labs, colony and sometimes develop and build devices for other universities.

Project Examples

An example of a highly complex device developed by the Bioengineering division is a “manipulandum” for Dr. Eb Fetz and partners. The researchers’ central goal is to learn how our brains control our arms in the complex activities that seem so effortless for the able-bodied. Our NHP subject is trained to grasp a handle in the device, and through it apply torques, forces and motions in various directions in order to move a cursor on a display screen (and receive rewards for performing the task properly). Extracellular nerve signals from various areas within the brain and spinal cord are measured during these activities. Some of the earliest of these devices were only capable of controlling a single parameter (flexion-extension torque). Our latest versions measure up to seven orthogonal forces and torques, move under power in two axes, and can simulate more realistic phenomena like inertia. This requires sophisticated mechanical, electronic, and firmware design and implementation.

The manipulanda are exceptional while most of our devices are far simpler. We repair damaged equipment (from fixing bad power cables and stuck set-screws to complex systems), make recommendations of materials and commercially-made products, and diagnose subtle technical problems (including noise), as well as develop new devices. We stock and resell a wide variety of parts and materials for urgent needs. Experiments that are “down” due to faulty equipment are always our top priority.

Experienced Staff

Being in research requires a never-ending stream of new experimental designs, and coping with our clever nonhuman primate (NHP) subjects who come up with new ways to thwart the best plans.Bioengineering’s most important asset in solving these problems is our people, who have years of experience solving practical problems with the equipment used in experimental studies involving NHPs.  They are able to share solutions to problems common to research groups.

The WaNPRC in-house machine shop, designs and builds devices from metals, plastics and other materials using a variety of precise machining, welding, and other technologies. For devices requiring complex shapes or repeated machining operations, we have a 4-axis CNC milling machine. We also make use of local companies for special operations that are beyond what we can achieve in our facilities, such as: 3-D printing, anodizing, water-jet cutting, and forming large pieces.

The WaNPRC electronics shop designs and builds devices for measurement, control, and communications. Increasingly these are compact and made with surface-mount technology, and can have varying degrees of “smart” microcontrollers in them and consume very little (battery) power. We’ve developed electro-optical systems for stimulation and control, and telemetry systems for situations where interconnecting wires are intolerable.

Cost

While these services are not free, their cost is significantly reduced by P51 grant funding from the National Institutes of Health. Most similar services on the University of Washington campus charge at least twice our labor rate, which is currently $47 per hour, and those shops do not have our experience with NHP research. Parts and materials are sold at cost. Project costs can be estimated before any work is commissioned – though creating firm estimates takes time and will add to the total cost. We’re currently developing some tools that will provide regularly e-mailed status reports for longer projects. Please let us know if we can assist with your next project.

Frank Miles | Research Engineer | WaNPRC Division of Bioengineering

The Washington National Primate Research Center supports outstanding research directed towards significant human health issues and nonhuman primate health and biology. In order to accomplish this mission, we carefully monitor the health and well-being of our animals. We are proud of the high quality animal care that is provided by our personnel. The BioBulletin newsletter will include interviews with various staff to help explain their roles in the Center’s scientific mission.

The following are interviews with two of our supervisory veterinarians, who are tasked with leading our animal care program.

 

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Interview with Dr. Lane, DVM

What is your roll as a veterinarian at the Center?

As a primate Veterinarian I look out for the health and well-being of our animals. They deserve the best possible care and I strive to provide that to them. I work with many groups to accomplish that goal including our animal care staff, veterinary technicians, behavioral management group and research support staff. Veterinarians provide preventative health care such as twice yearly physical exams with routine blood work as well as surgical and emergency care. Working with primates is always challenging and interesting and no two days are ever the same. We try to develop inventive ways to deliver their medications and provide them with healthy treats which they almost always appreciate!

How do you support the research conducted at the Primate Center?

As a Supervisory Veterinarian, I help to ensure we have adequate staff and resources to provide anesthesia support for the projects as well as general clinical care for the nonhuman primates enrolled in studies. I am available to the PI’s to consult on upcoming projects and assist with study design and planning. I also participate by providing surgical, clinical and after hours support. I am passionate about the research and proud to have been a part of some very important advances in healthcare.

What challenges are you working to overcome?

It is always a challenge to meet ever increasing demand for personnel resources. The Vet Staff are experts at being two places at once!

In what ways are you improving operational efficiency?

Team building and cross-training are critical to having a program that can run smoothly under any circumstances. I have enjoyed working with staff members from many different areas of the center towards these goals. I am also working closely with our Associate Director, IT staff and other teams on upgrades to our electronic record system. These improvements will save our Vet Staff valuable time that can be better devoted to caring for the animals.

What are your vet-related goals for 2016 and the future?

I hope to continue to expand our capabilities by recruiting highly qualified candidates to the Center. Equally as important is promoting continuing education and training opportunities for our staff. Ultimately, our goal every day is to do the very best we can do for these animals and continue supporting the important work we do here at the Center.

What should Center personnel and the public know about animal care at the Primate Center?

The people that care for the animals at the center are highly dedicated and compassionate individuals. Their 24/7 commitment to the well-being of these animals is critical to the ultimate goal of finding cures and saving lives. It is truly a labor of love that the public does not get the opportunity to hear a lot about.

Is there anything else that you’d like to say in the BioBulletin newsletter?

I have had the opportunity to work at other National Primate Research Centers during my career and I am proud to be back in the family again. The work done here is critical to our global health and I want everyone to understand the level of compassionate care that goes into it. It takes remarkable people to take care of these very special animals.

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Interview with Dr. Barras, DVM

What is your roll as a veterinarian at the Center?

My primary role as a veterinarian is to safeguard the processes the Center has put into place to ensure the welfare of the animals within its facilities. While part of this role includes acting in the capacity of a clinical veterinarian, the majority of my time is dedicated to making sure that the environment in which the animals live not only meet the regulatory standards, but also meet the high standards for animal care that is set forth by the Center. In short, my role as a veterinarian at the Center is to be an advocate for the animals housed within the facilities.

What challenges are you working to overcome?

One of the biggest challenges that I face is that of communication. While this is a very broad challenge it impacts animal health on a daily basis. Here are a few examples. The first being simple communication regarding animal needs. We are currently in the process of modeling the quickest and most reliable way to communicate a need of an animal or group of animals from the person who recognizes that need to the person who can take action and accomplish the task.

A second example would be data retention and subsequent viewing or sorting. Just as there has been an initiative in human medical record keeping to have better access to ensure physicians are fully informed about a patient’s history so that the best decisions can be made for that patient, so is it with animal record keeping. It is paramount that animal records are easily accessible at all times so that veterinarians and staff members are fully informed to make the best decisions for the welfare of each animal. The information technology unit of the Primate Center spends countless hours every week to ensure that the staff has all the needed information at the tip of their fingers.

In what ways are you improving operational efficiency?

Streamlining decision making and communication will allow for the largest positive impact on animal welfare.

What are your vet-related goals for 2016 and the future?

My primary goal for 2016 is to construct a state of the art animal holding and breeding building at the Arizona facility.

What should Center personnel and the public know about animal care at the Primate Center?

While the Primate Center has some of the highest standards for animal care, it is the staff members who interact with these animals every day that make these standards come to life. An institution can have the best rules and regulations, but it requires a knowledgeable, caring and dedicated staff to achieve achieve success in animal care.