Neural circuits for stress responses and emotional learning: organization and postnatal development.
The ability of animals to mount adaptive responses to emotional and physiological stress is mediated by central neural pathways that control neuroendocrine secretion, autonomic function, and motivated behavior. The long-term objective of Dr. Rinaman's research program is to characterize the functional multisynaptic organization of these neural systems. Neuroanatomical, physiological, and behavioral techniques are applied to probe these circuits in developing and adult animals, which display marked differences in homeostatic responses to various stress stimuli. This research program offers unique opportunities to test hypotheses about brain structure-function relationships within the natural context of nervous system development.
Ongoing studies in the laboratory analyze stimulus-induced expression of the immediate-early protooncogene c-fos (a marker of neural activation) in rats after exposure to various stress- and anxiety-provoking challenges. Analysis of c-fos expression is combined with retrograde labeling of central neural pathways and immunocytochemical detection of neurotransmitter chemicals to characterize the axonal projections and chemical phenotypes of stimulus-activated cells. These experiments focus on the functional roles played by central noradrenergic and peptidergic neural circuits in developing and mature rats. Another ongoing project uses live neurotropic viruses for transneuronal tracing of multisynaptic neural circuits as they become synaptically linked during postnatal development, and examines the ability of early life events to perturb normal patterns of synaptogenesis in limbic-autonomic brain circuits. Other experiments measure changes in hormone secretion and behavior to assess the impact of various physiological and pharmacological stimuli on centrally-mediated stress and anxiety responses.
L. Rinaman. Invited Review. Hindbrain noradrenergic A2 neurons: diverse roles in autonomic, endocrine, cognitive, and behavioral functions. American Journal of Physiology Regulatory Integrative and Comparative Physiology. In press (2010).
T.J. Koehnle and L. Rinaman. Early experience alters limbic forebrain Fos responses to a stressful interoceptive stimulus in young adult rats. Physiology & Behavior 100 (2010) 105-115. PMID: 20159026
Banihashemi, L. and Rinaman, L. Repeated brief postnatal maternal separation enhances hypothalamic gastric autonomic circuits in juvenile rats. Neuroscience 165: 265-277, 2010.
Weber, B.C., Manfredo, H.N., and Rinaman, L. A potential gastrointestinal link between enhanced postnatal maternal care and reduced anxiety-like behavior in adolescent rats. Behavioral Neuroscience 123: 1178-1184, 2009.
Bienkowski, M.S. and Rinaman, L. Noradrenergic inputs to the paraventricular hypothalamus contribute to hypothalamic-pituitary-adrenal axis and central Fos activation in rats after acute systemic endotoxin exposure. Neuroscience 156: 1093-1102, 2008.
Card, J.P., Levitt, P., Gluhovsky, M. and Rinaman, L. Early experience modifies the postnatal assembly of autonomic emotional motor circuits in rats. Journal of Neuroscience 25: 9102-9111, 2005.