William E. Cullinan, Ph.D.

John P. Raynor Professor
Anatomy and Neurobiology

Schroeder Complex 416

(414) 288-6764

E-mail

Dr. Cullinan received his Ph.D. degree from the University of Virginia in 1991.  He also did a post-doctoral research fellowship at the University of Michigan from 1991-95. He joined the Marquette faculty in 1995.

Research

Research in my laboratory is directed at understanding the neurobiology of stress in the context of neuronal circuits. We are particularly interested in understanding the link between stress and psychiatric illness. The ability to cope with changing internal or external environmental demands (i.e. stress) is critical to the survival of all organisms. In mammalian systems this capacity is known to involve the hypothalamic-pituitary-adrenol
(HPA) axis. Stress-mediating neural inputs converge upon a final common pathway, the origin of which is known to be a collection of neurons in the hypothalamic paraventricular nucleus. 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 have focused on: a) defining neurotransmitter-specific sources of input to the CRH-containing neurons of the hypothalamic paraventricular nucleus which are engaged in response to various forms of acute and chronic stress, b) characterization of brain pathways which mediate corticosteroid feedback inhibition of the stress response, c) 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, and d) functional genomic analyses of brain structures implicated in the stress and/or steroid regulation. An integrated technical approach is 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:

1. 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.
2. 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.
3. 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.
4. Ziegler DR. Cullinan WE. Herman JP. (2002) Distribution of vesicular
   glutamate transporter mRNA in rat hypothalamus. Journal of Comparative
   Neurology. 448(3):217-29.
5. 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.
6. Cullinan, W.E., and Wolfe, T.J. Chronic stress regulates levels of mRNA
   transcripts encoding beta subunits GABA-A receptor in the rat stress
   axis. Brain Research. 887:118-124.
7. Raff, H., and Cullinan, W.E. (2000) Hypothalamus and Endocrine System, In: Neuroscience Secrets, (Wong-Riley ed.) Hanley-Belfus:Philadelphia.
8. 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.