Rita J. Valentino, Ph.D., Professor Director, Division of Stress Neurobiology
Dr. Valentino has been studying the mechanisms by which stress leads to psychopathology since 1985. Her scientific contribution has been to show that corticotropin-releasing factor (CRF), the orchestrator of the stress response, serves as a neurotransmitter to modulate the activity of the biogenic amine systems, the locus ceruleus-norepinephrine system and the dorsal raphe (DR)-serotonin (5-HT) system. As both of these systems have been implicated in affective disorders, her studies on CRF interactions with these systems provides a window into how stress increases vulnerability to these diseases. The neurobiological basis for sex and developmental differences in stress reactivity and stress-related disorders are recent directions of the laboratory. Her laboratory uses electrophysiological approaches to characterize how stress affects activity of biogenic amine neurons and functional neuroanatomy to identify the circuitry by which CRF communicates with these neurons. They also use cellular and molecular approaches to elucidate how chronic stress can produce enduring changes in the monoamine systems. In addition, a branch of her research is focused on central control of pelvic visceral function. To this end, the laboratory identified a neural circuit through which pelvic visceral activity and cortical activity are coordinated and that may also account for the co-morbidity of psychiatric and pelvic visceral symptoms.
Sheryl G. Beck, Ph.D., Associate Professor
Dr. Beck is investigating the cellular mechanisms underlying individual vulnerability to stress as well as stress resilience. The primary focus of the research conducted in the laboratory is on the serotonin (5-HT) limbic system as well as arousal systems that include Orexin neurons and the locus coeruleus (LC). Both behavioral models and genetically engineered animal models are used in concert with a battery of behavioral tests, electrophysiological recording techniques (including in vivo extracellular, extracellular single unit in vitro and whole cell) and immunohistochemistry and morphology. Over the years Dr. Beck's laboratory has demonstrated that characteristics of 5-HT mediated responses are very much dependent upon where they are recorded, i.e., different subfields of the hippocampus or raphe, and that there is differential modulation of both neuron characteristics as well as receptor mediated responses, depending upon the stressor, genotype, as well as the brain area under investigation. Most recently Dr. Beck's laboratory has demonstrated that there are very different 1) characteristics of 5-HT neurons within the subfields of the dorsal raphe and median raphe, 2) receptor mediated responses within the subfields of the raphe, 3) excitatory and inhibitory input to the subfields, 4) morphology of the neurons, and 5) their modulation by genetically manipulated mouse models of anxiety or behaviorally stressed mouse models. In addition, they have demonstrated that the locus coeruleus is also altered by stress. The firing rate of the LC neurons, the stress hormone corticotrophin releasing factor, Orexin, and kappa agonists all have altered responses in a rat model that is hyper-responsive to stress, i.e., WKY. Further research in this field will continue to delineate the complex circuitry within the raphe, as well as between the raphe and its forebrain targets. The goal of the lab is to identify cellular markers of stress resiliency as well as determine those aspects of the 5-HT-limbic system circuitry that are altered by acute or chronic stress, leading to mood disorders.
Seema Bhatnagar, Ph.D., Assistant Professor
Dr. Bhatnagar is interested in how individuals adapt to chronic stress and in determining how the ability to adapt contributes to resilience or vulnerability to the deleterious effects of stress. She is also interested in how stress exposure during different developmental stages produces long-lasting changes in neural circuits underlying behaviors related to anxiety and depression. Her work is focused on components of thalamic-limbic circuitry that regulate adaptation to stress and she uses systems-level approaches to address these questions.