Our Mission and Faculty
The broad goals of the latboratory are to:
- Define cross-species similarities and differences in the normal anatomy of structures engaged in stress and coping behaviors, including the amygdala, extended amygdala, hypothalmus, limbic and serotonin system.
- Create reliable and naturalistic animal models of chronic stress for both infant and adult animals.
- Create reliable coping paradigms that lower stress (measured by hormonal and behavioral outcomes)
- To examine structural and chemical changes in
- the serotonin system,
- glucocorticoid system,
- neuroplastic markers after stress.
- To develop stress paradigms applicable to humans and primates in order to begin to identify 'stress-vulnerable' curcuits in human populations.
Ultimately, our goal is to better understand how stressors may differentially affect vulnerable human populations, and the brain regions mediating the aberrant responses in this population. By better understanding the circuitry and the transmitter systems modulating important ‘stress’ circuits we can approach development of behavioral and medication paradigms that specifically target them.
Julie Fudge, MD
The amygdala is a major limbic structure that is involved in the emotional coding of environmental stimuli. In particular, the amygdala is activated by threatening or fearful stimuli in humans. In mood and anxiety disorders, the amygdala is hyperactivated, suggesting aberrant ‘overcoding’ of negative stimuli. Our work has shown that the amygdala is characterized by unique connections to the monoamine systems. In particular, key output regions of the primate amygdala such as the central nucleus are strongly innervated by the serotonin system, indicating a major pathway for control of anxiety behaviors by serotonin enhancing drugs (SSRIs). These same output paths have direct connections to the hypothalamic-pituitary-adrenal axis, providing a way for emotionally relevant information in the external milieu to directly affect the ‘stress axis’. Another line of research is to characterize amygdala cell populations that have an immature phenotype. These cells reside in the subventricular zone near the lateral horn of the ventricle in primates, and contain a number of markers typical of immature neurons. They are richly innervated by serotonin containing fiber, suggesting that serotonin plays a role in their survival and growth. Our goal is to determine the distribution and development of these cells across the lifespan, and determine their responsiveness to treatment interventions in primate models.
Dana Helmreich, PhD
My broad research emphasis is on the hormonal and behavioral sequelae of stress, and how these outcomes may be altered by effective coping mechanisms, such as perceived control and voluntary exercise. These active coping behaviors may promote resilience in the presence of ongoing stressors. Currently my research, using adult rats, is focused on changes that occur in hypothalamic neurons that control both the hypothalamic-pituitary-adrenal axis and the hypothalamic-pituitary- thyroid axis in animals that have the opportunity to perform active coping behaviors and in animals in which these behaviors are prevented. Additionally, we are initiating studies to determine how stress and coping alter amygdaloid neural circuits and associated behavior.
David Parfitt, PhD
One aim of our behavioral neuroendocrinology laboratory is to understand how early life stressors alter brain mechanisms that ultimately alter physiology and behavior long-term. We are currently developing a mouse model to explore the impact of neonatal rearing environment on offsprings’ future susceptibility or resilience towards future stressful situations. Our research laboratory utilizes a whole animal approach with a variety of techniques to elucidate how early life stressors alters behavior (maternal behavior towards the developing pups as well as behavior of the offspring), hormone secretion (adrenocorticotropin hormone, corticosterone, etc.), and protein and mRNA expression (for markers of neuronal activation and regulators of the hypothalamic-pituitary-adrenal axis) within the brain. Once this mouse maternal separation paradigm is established, we will take advantage of the powerful genetic tools available in the mouse (including knockout and transgenic technologies) to determine the interaction between environment, genetic, and epigenetic factors governing brain development. This basic research has clinical biomedical relevance as increasing evidence in humans suggests that early adverse experience contributes to the vulnerability for a variety of psychopathologies particularly depression.
