Date of Award


Document Type

Honors Thesis


Basic Biomedical Science

First Advisor

Dr. Patrick J. Ronan

Second Advisor

Dr. Kenneth R. Renner

Third Advisor

Dr. Cliff H. Summers


Orexin, CRF, Immunohistochemistry, Stress, Anxiety

Subject Categories

Social and Behavioral Sciences


A Novel Indirect Pathway of CRF Innervation to Perifornical Orexin Neurons is Relayed Through the Lateral Septum

Timothy D. Skog

Director: Patrick J. Ronan, PhD

Orexin (Orx) and corticotropin releasing factor (CRF) play integral, sometimes parallel, roles in a host of arousal/stress responses. These neuromodulators have been implicated in a variety of stress-induced psychiatric disorders including addiction and affective disorders. Previous work has indicated that these systems interact and regulate each other—perhaps providing a feed-forward mechanism for enhancing and fine-tuning stress responses. This is implied by the fact that orexinergic neurons in the hypothalamus receive innervation from many CRF-rich neuronal fields including the paraventricular nucleus of the hypothalamus (PVN), bed nucleus of the stria terminalis (BNST) and central nucleus of the amygdala (CeA). We sought to clarify if these CRF afferent pathways include CRF neurons and to determine whether these inputs have any topographical organization. To accomplish this, we used a combination of neuronal tracing methods and immunohistochemistry to visualize the distribution and anatomy of these systems in various brain regions. We provide further evidence that CRF neurons in these regions specifically project to Orx neuron fields, as well as describe a novel circuit pathway for indirect CRF innervation of orexinergic neurons in the hypothalamus through the lateral septum. There appears to be specific topographic distribution of inputs supporting the hypothesis that perifornical Orx neurons preferentially contribute to stress and anxiety responses.



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