Neural circuits for stress responses and emotionality: organization and interactions with diet and body energy balance
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 rodent species under different metabolic and dietary conditions (e.g., after an overnight fast, or after maintenance on a high-fat diet) that markedly shift homeostatic responses to stress. This research program offers unique opportunities to test hypotheses about brain structure-function relationships.
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 that link brainstem regions with the hypothalamus and limbic forebrain. Another ongoing project uses live neurotropic viruses for transneuronal tracing of multisynaptic neural circuits that regulate food intake. 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.
Zheng, H., Stornetta, R.L., Agassandian, K. and Rinaman, L. Glutamatergic phenotype of glucagon-like peptide 1 neurons in the caudal nucleus of the solitary tract in rats. Brain Structure & Function (2014) In Press. PMID: 25012114
Kreisler, A.D., Davis, E.A. and Rinaman, L. Differential activation of chemically identified neurons in the caudal nucleus of the solitary tract in non-entrained rats after intake of satiating vs. non-satiating meals. Physiology and Behavior (2014) In Press. DOI: 10.1016/j.physbeh.2014.01.015
Zheng, H., Cai, L. and Rinaman, L. Distribution of glucagon-like peptide 1-immunopositive neurons in human caudal medulla. Brain Structure & Function (2014) DOI 10.1007/s00429-014-0714-z PMID: 24510283
Maniscalco, J.W. and Rinaman, L. Systemic leptin dose-dependently increases STAT3 phosphorylation within hypothalamic and hindbrain nuclei. American Journal of Physiology Regulatory Integrative and Comparative Physiology 306 (2014) R576-R585. PMID: 24523344
Bienkowski, M.S., Wendel, E.S. and Rinaman, L. Organization of multisynaptic circuits within and between the medial and central extended amygdala. Journal of Comparative Neurology 521 (2013) 3406-3431. PMID: 23640841
Maniscalco, J.W., Kreisler, A.D. and Rinaman, L. Satiation and stress-induced hypophagia: examining the role of hindbrain neurons expressing prolactin-releasing peptide (PrRP) or glucagon-like peptide 1 (GLP-1). Frontiers in Neuroscience 6 (2013) article no. 199. PMID: 23346044
Maniscalco, J.W. and Rinaman, L. Overnight food deprivation markedly attenuates hindbrain noradrenergic, glucagon-like peptide-1, and hypothalamic neural responses to exogenous cholecystokinin in rats. Physiology & Behavior 121 (2013) 35-42. PMID: 23391574
Zheng, H. and Rinaman, L. Yohimbine anxiogenesis in the elevated plus maze requires hindbrain noradrenergic neurons that target the anterior ventrolateral bed nucleus of the stria terminalis. European Journal of Neuroscience 37 (2013) 1340-1349. PMID: 23368289