Research
The Prairie Vole Model
A prairie vole family in their nest
Prairie voles are small rodents that look similar to mice (but have a shorter tail and flatter ears than mice). These rodents are interesting to us because they display social behaviors that are similar to humans. In their natural environment, these animals live in family groups, with a mother, father, and children all living together. Adult prairie voles form very strong social bonds (for instance, family bonds, opposite-sex bonds) that are difficult to break. Also, some (but not all) prairie voles mate monogamously, similar to the way humans mate. We study social behavior in the prairie voles, as well as how social experiences interact with other behaviors, the brain, endocrine system, immune system, and heart.
Ongoing Research Themes
Theme 1: Negative Health Effects of Social Stress
The Behavioral and Physiological Consequences of Vicarious Stress
Stress seems to be an inescapable aspect of modern life. Whether it is worrying about your next test or the presentation that you have to give next week, our bodies are constantly in a state of high arousal. But what if you aren’t the one who is taking the test? What if it’s your significant other or friend who is experiencing stress? Can just being around or witnessing someone in a high-stress situation be enough to stimulate your own stress response? We are attempting to answer these questions by using prairie voles in a controlled laboratory setting. To do this, we will expose one of a sibling pair of voles to a stressor and allow the other animal to observe. It is our hypothesis that the animal that is observing the other animal in the stressful situation will exhibit higher than normal levels of circulating stress hormones, possibly as high as the animal actually undergoing the stressful situation. These findings would support the idea that the mere act of witnessing a stressful event or being around someone who is stressed can cause the observer to exhibit signs of stress.
Effects of Social Stress in Aging Animals
Social support has been shown to provide a buffer against negative effects of social and environmental stress such as impaired cardiovascular function, higher rates of depression and anxiety, and an increased stress response. However, there has been little research investigating this relationship in an aging model. To assess this long-term buffering effect, the highly social prairie vole is used as they are a socially monogamous species that tends to mate for life, similar to humans. Male and female prairie voles are paired together and allowed to breed until they reach old age and no longer are producing litters. Animals are then assessed for behavioral changes, stress reactivity, and the ability of one animal to buffer the stress of their socially-bonded partner. This current research project will help to shed more light on whether aging males and females respond differently to stress, and highlights the importance of social bonds and their beneficial effects against stress throughout the aging process. (Picture from: http://traumatoolkit.blogspot.com/2011/11/hpa-axis-trauma-and-you.html).
Social Stress, Behavior, and Neurobiology
Social relationships positively influence psychological and biological function. The disruption of social bonds through separation or death often results in bereavement and can contribute to depression and cardiovascular disease. Social isolation in prairie voles results in depressive behaviors, increased heart rate, and autonomic imbalance. Several of our ongoing studies are focused on these negative consequences. This research involves several measures of behaviors, including social behaviors, anxiety- and depression-related behaviors, exploratory behaviors, and stress coping behaviors. Coupled with these behavioral measures, this research involves physiological measures, such as stress hormones, immune function, autonomic and cardiac function, vascular function, and gut bacteria. Our research also includes neural measures, including cellular functions, genes, and peptides. This research informs our understanding of the negative consequences of social stress, which can aid in our ability understand how social experiences influence human health.
Theme 2: Developmental Consequences of Social Stress
Influence of Early Life Stress on Behavioral and Emotional Development
The prairie vole is a valuable model for investigating the influence of early life stress on social and emotional development. This ongoing project is focused on the effects of social isolation during the juvenile period of development. The design models early life social stress in humans, representing childhood through the early teenage years. Following exposure to social isolation in juvenile prairie voles, animals are evaluated for pro-social and play behaviors during the juvenile stage, as well as emotion-related behaviors and stress responses during adulthood. Using several behavioral and physiological measures, this study will provide valuable knowledge about the consequences of social stress on developmental processes. This study will inform our understanding of the impact of early life social experiences on the risk of mood and anxiety disorders, stress coping abilities, and social competence.
Protective Effects of Mild Stress During Early Life
The prairie vole is a valuable model for studying methods to protect against social stress. This ongoing project compares the efficacy of various forms of stress inoculation early in life, to determine whether these methods can protect against social stress later in life. Stress inoculation is analogous to a vaccine, where small “doses” of mild stress might help to prevent the manifestation of stress-related problems later (such as depression or anxiety). Using a variety of behavioral and physiological tests, this project will inform our understanding of how different forms of mild stress during early life might protect against more severe stress during adulthood.
Theme 3: Prevention and Treatment Strategies for Social Stress
Effectiveness of Antidepressant Treatment for Social Isolation
The goal of this study is to investigate whether treatment with antidepressant drugs (such as serotonin reuptake inhibitors) can protect against deleterious cardiac and behavioral changes induced by social stress. This is an important consideration because social isolation is associated with an increased mortality risk, especially in people with health issues such as cardiovascular disease. This ongoing research is investigating whether antidepressant drugs can improve measures of heart function and behavioral responses during stress in socially isolated male prairie voles. This investigation and future similar projects will inform our understand of the mechanisms through which the brain changes during both stress and treatment. The novel experiments conducted in this animal model will improve our understanding of how negative social experiences adversely influence mood, cardiovascular regulation, and quality of life, and can lead to improved treatments for individuals experiencing social stress. Thank you to Pfizer for the generous donation of Zoloft (sertraline hydrochloride), which was used in some previous research on this topic (awarded to Neal McNeal for use in his dissertation project). (Picture from: http://www.pfizer.com/products/product-detail/zoloft).
Treating Isolation with Environmental Enrichment
The disruption of social bonds in humans can significantly affect mental health, specifically mood and emotion. Environmental enrichment that stimulates the brain (such as cognitive activities and exercise) may be beneficial for individuals who suffer from the consequences of social isolation. This ongoing resarch is investigating the hypothesis that environmental stimulation can protect against the negative effects of social isolation using prairie voles as an animal model. We are studying prairie voles in different social environments, with or without an enriched environment, as well as various forms of enrichment (such as enrichment that specific includes physical exercise and enrichment that does not include exercise). Using several measures of behavior cardiovascular function, and central nervous system processes, this research helps us understand how stimulation from the environment can prevent or treat the consequences that result from social isolation in humans.
Can Exercise Counteract Social Stress?
Disruption of the social environment has been shown to negatively influence psychological and physiological functions in humans and rodents. The focus of this ongoing research is to assess the degree to which exercise may counteract the negative effects of social isolation and stress on behavior, physiology, and the brain. To investigate this relationship, prairie voles in various housing conditions (such as isolated housing, paired housing with a family member, paired housing with an opposite-sex partner) are allowed access to a running wheel in their home cage (versus sedentary conditions, without access to a running wheel). Using several behavioral and neurobiological methods, this experiment will further our understanding of the complex relationship between psychological and physiological health, and provide insight for humans who find themselves in prolonged periods of social or environmental stress.
Specific Research Methods
Pro-Social and Play Behaviors
Many animals engage in some type of play behavior when they are young. These behaviors may be observed in human children on a playground or in social settings. Play is an incredibly important part of development and can be systematically measured in juvenile animal models. Play behaviors in rodents include several types of social interactions. These may include chasing, where one animal pursues another; pouncing and pinning, which involve one animal pouncing on to the other animal from an upright position and pinning the other animal to the ground while the receiving animal assumes the supine position; and boxing or wrestling, where one animal assumes the upright position and paddles their forepaws toward the other animal, often resulting in tumbling and pinning behaviors. Collectively, these pro-social play behaviors constitute are an integral part of early life socialization in rodents.
Stress Inoculation
Sometimes mild stress can be protective and build resilience – this is the process of stress inoculation. A technique to potentially promote stress inoculation is picking up prairie voles and placing them briefly in a cup. The prairie vole is then left in the cup for 30 seconds to induce a controlled, mild stress situation. The theory of stress inoculation is that the exposure to a small amount of stress encourages resilience that carries into adulthood. This method allows for an analysis of how the mild stress may protect against more severe stress later in life, such as social isolation or other negative social interactions.
Depressive Behaviors
How to study "depression" in rodents?
We study several behaviors in the prairie voles, including behaviors that relate to depression and other mood disorders. For instance, the forced swim test is used as a measure of depressive behaviors in rodents. An animal is placed into a tank of water for a brief period, and its behavior is observed. Animals that respond in a passive manner to this test (for instance by floating instead of actively swimming around the tank) are showing a sign of depression. By observing the animal’s stress-coping strategies during this test, we are able to gain an understanding of its behavior. (Picture from: http://www.sciencedirect.com/
science/article/pii/S0165614702020175).
science/article/pii/S0165614702020175).
Anxiety Behaviors
Elevated plus maze
We study behaviors related to anxiety in the prairie voles. The elevated plus maze is a plus-shaped maze that is elevated off of the ground. The maze has two opposing open arms of clear Plexiglas and two opposing arms that are protected by tall black walls. The animal is placed in the center of the maze and allowed to explore it for a brief period. We can then calculate the amount of time an animal spends in the open versus closed arms of the maze. Animals that are experiencing more anxiety spend little time exploring the open arms, and instead spend quite a bit of time in the closed, protected arms of the maze.
Cardiovascular and Autonomic Function
Telemetry transmitters
Using radiofrequency technology, we can study continuous cardiovascular and autonomic function in the prairie voles. After anesthetizing an animal, a small transmitter is implanted into its abdominal cavity. Leads from the device are positioned just below the surface of the skin to either side of the animal’s heart which gather and transmit cardiovascular data (using radio signals) to the computer. With this technology the computer creates an electrocardiographic (ECG) signal, allowing us to study the functioning of the heart. Because this technology is wireless, it is possible to study cardiovascular function in prairie voles during different behavioral tasks (such as the forced swim test or the elevated plus maze, described above). This can provide useful information about the integration of behavior and cardiovascular function.
Vascular and Endothelial Function
Blood vessel function
The functioning of the heart is directly related to the functioning of the blood vessels. Newer technology, involving the study of vascular contractions and relaxation ability, endothelial cell function, and blood pressure, can inform our understanding of how stress, behavior, and social experiences influence the progression of hypertension, atherosclerosis, or cardiovascular disease. (Picture credit: http://arterialhealth.net/physicians/physician-information/).
Immune Function
Studying bacteria
The immune system can be significantly affected by stress, behavior, and social experiences. Some of our studies include a focus on innate immunity or adaptive immunity. We can use these results to inform our understanding of both general immune function and specific immune system cells and factors that might be altered in the context of stress. (Picture credit: http://turtleresearch.files.wordpress.com/2011/08/dsc_0123.jpg).
Stress Hormones and Endocrine Function
Hormone levels in the circulation
Following behavioral procedures and physiological experiments, plasma can be analyzed for hormones and other chemicals associated with stress, behavior, emotion, and cardiovascular function. These analyses allow us to make inferences about the relative activity of those hormones and chemicals, and how they are influenced by behavior and the environment. For example, circulating corticosterone levels are used as an index of stress in rodents. This graph is showing higher corticosterone levels in prairie voles that have been exposed to social isolation (versus animals that are paired in a cage with a sibling), suggesting that isolated prairie voles are experiencing a higher level of stress.
Central Nervous System
Cells in the hypothalamus
In some studies, we analyze the functions of cells and neurotransmitters in the brain. Using antibodies, chemicals, and specific staining procedures, we can observe different cells in the brain of prairie voles that have been exposed to different behavioral tests or social situations. We can use this information to learn how the brain controls behavior or specific peripheral nervous system processes (such as cardiovascular function).
Environmental Enrichment
Example of an enriched environment
Environmental enrichment (EE) refers to creating a more complex habitat in which the prairie voles can live. EE can include toys, a larger cage, running wheels for exercise, social interaction, music, nesting material, as well as other items. Animals who live in an enriched environment will have increased synaptic activity. We have provided some of our voles with EE cages with the hypothesis that the enriched environment will help the prairie voles perform better on stress tests. We will compare isolated prairie voles in an enriched environment to isolated prairie voles in a standard lab cage to see if the EE group shows lower stress levels. We will also compare isolated prairie voles in EE cages to pair-housed voles to see if the enriched environment will provide some of the stimulation that the prairie voles miss when they are isolated.
Physical Exercise
Exercise
Physical exercise may be protective for the body in many respects, including conferring benefits for our muscles, heart, and brain. Exercise may be a useful treatment for several conditions such as depression, anxiety, and heart disease. Using the prairie vole model, we are investigating the potential stress-buffering effects of exercise on behavior, the cardiovascular system, and the brain in the context of social stress. (Picture from: http://www.mindsparke.com/brain-training-blog/brain-exercises/brain-fitness-neurogenesis-and-social-contact/).
Exploratory Behaviors
Open field
Many of our studies investigate specific behaviors in prairie voles. The study of exploratory behaviors can inform our understanding of an animal's willingness to investigate a novel environment. One example is the open field test, which can be used to study various behaviors such as general exploration, forward and backward motion, movements in the center section vs. surround section of the open arena, and grooming. In addition to exploration, the open field test can also provide insight into anxiety-related behaviors in prairie voles exposed to social stress.
Vicarious Stress
To effectively study how stress might transmit vicariously between animals, our projects required the development of a novel testing apparatus. Most behavioral tests focus just on one animal at a time. For this study, we are interested in behavioral and physiological measures of stress response activation in two animals experiencing a stressor from two different perspectives (i.e., direct and observed). To accomplish this, we have combined two validated behavioral tests into a single testing apparatus, the tail-suspension test and the open field test. In the experimental group, one animal is directly exposed to a stressor (i.e., suspension by the tail for five minutes, the “model”) while another animal passively observes within the same testing apparatus (i.e., on the bottom of the open field chamber allowed to move around freely, the “observer”). The control group is identical to the testing group with the exception that the two animals are tested alone in separate apparatuses located within two different rooms. This paradigm allows us to draw strong conclusions, not only about the behavioral and physiological effects of vicarious stress, but also the stress attenuating effects of social buffering.