Research in the Cullinan Lab

Research in my laboratory is directed at understanding the neurobiology of stress and the link between stress and psychiatric illness. The ability to cope with changing internal or external environmental demands (i.e. stress) is known to involve the hypothalamic-pituitary-adrenal (HPA) axis. Stress-mediating neural inputs converge upon a final common pathway, the origin of which is known to be the CRH-containing neurons in the hypothalamic paraventricular nucleus (PVN). Activation of these neurons results in a cascade of events culminating in the release of adrenal corticosteroids. Chronic elevated corticosteroid levels have been linked to illnesses such as major depression.

Recent efforts in our lab have focused on: 1) defining neurotransmitter-specific sources of input to the CRH-containing PVN neurons, 2) characterization of brain pathways which mediate corticosteroid feedback inhibition of the stress response, 3) understanding the regulation of key molecules within defined stress-related pathways following chronic stress conditions, which are characterized by elevated basal and stress-induced corticosteroid levels, d) understanding dysregulation of the HPA axis following traumatic brain injury, and e) effects of deep brain stimulation (DBS) in a model of depressive illness. Integrated technical approaches are taken to these issues, including combinations of neuroantomical tract-tracing methods, immumocytochemical and hybridization histochemical techniques, in vivo pharmacology, as well as biochemical, behavioral, molecular biological, and molecular surgical approaches.

Selected Publications

• Ziegler, DR, Edwards, MR, Ulrich-Lai, YM, Herman, JP, Cullinan, WE (2012) Brainstem origins of glutamatergic innervation of the rat hypothalamic paraventricular nucleus. J Comp Neurol. 520(11): 2369-94.
• Ulrich-Lai, YM, Jones, KR, Ziegler, DR, Cullinan, WE, Herman, JP (2011) Forebrain origins of glutamatergic innervation to the rat papaventricular nucleus: differential inputs to anterior vs posterior subregions. J Comp Neurol. 519(7): 1301-19.
• Cullinan, W.E. (2009) Stress, In: Encyclopedia of Neuroscience, (Binder, Hirokawa, Windhorst, eds.), Springer: New York.
• Cullinan, W.E., Ziegler D.R., Herman, J.P. (2008) Functional role of local GABAergic influences on the HPA axis. Brain Structure and Function. 213:63-72.
• Raff, H., Jacobson, L. and Cullinan, W.E. (2007) Augmented hypothalamic coricotropin-releasing hormone mRNA and corticosterone responses to stress in adult rats exposed to perinatal hypoxia. J. Neuroendocrinolgy. 19:907-912.
• Ziegler, D.R., Cullinan, W.E. and Herman J.P. (2005) Organization and regulation of paraventricular nucleus glutamate signaling systems: N-methyl-D-aspartate receptors. J. Comp. Neurol. 484:43-56.
• Raff, H.R., Jacobson, L.J. and Cullinan, W.E. (2003) Elevated corticosterone and inhibition of ACTH response to CRH and ether in the neonatal rat: effect of hypoxia from birth. Am. J. Physiology. 285(5): R1224-30.
• Herman JP. Figueiredo H. Mueller NK. Ulrich-Lai Y. Ostrander MM. Choi DC. Cullinan WE. (2003) Central mechanisms of stress integration: hierarchical circuitry controlling hypothalamo-pituitary-adrenocortical responsiveness. Frontiers in Neuroendocrinology. 24:151-80.
• Ziegler DR. Cullinan WE. Herman JP. (2002) Distribution of vesicular glutamate transporter mRNA in rat hypothalamus. Journal of Comparative Neurology. 448(3):217-29.
• Herman, J.P., Tasker J.G., Ziegler D. R., and Cullinan, W.E. (2002) GABA, glutamate and gating: Role of the paraventricular nucleus microenvironment in stress integration. Pharmacology, Biochemistry, and Behavior. 71(3):457-468.
• Cullinan, W.E., and Wolfe, T.J. (2000) Chronic stress regulates levels of mRNA transcripts encoding beta subunits GABA-A receptor in the rat stress axis. Brain Research. 887:118-124.
• Cullinan, W.E. (2000) GABA-A receptor subunit expression within hypophysiotropic CRH neurons: A dual hybridization hybridization histochemical study. Journal of Comparative Neurology. 419(3):344-51.