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. Author manuscript; available in PMC: 2019 Jan 24.
Published in final edited form as: Front Neuroendocrinol. 2018 Jun 19;51:132–145. doi: 10.1016/j.yfrne.2018.06.003

Fig. 1. Orexin projections to stress-relevant brain regions.

Fig. 1.

This illustration depicts orexin neurons in the lateral hypothalamus (LH) and several stress-relevant projection sites. The expression of orexin receptors within these brain regions is also shown. Orexins are known directly innervate the prefrontal cortex (PFC) and Hippocampus (HIP), and orexin activation during stress underlie cognitive impairments. Orexin receptors in the Nucleus Accumbens (NA) and Ventral Tegmental Area (VTA) mediate stress-induced reward seeking. Orexins regulate activity in the hypothalamic pituitary adrenal (HPA) axis through projections to the paraventricular nucleus of the hypothalamus (PVN), where neurons expressing Corticotropin Releasing Hormone (CRH) are located. Further, orexin neurons densely project to the paraventricular nucleus of the thalamus (PVT), which plays a role in regulating neuroendocrine and behavioral adaptations to repeated or chronic stress. Orexins mediate behaviors relevant to affect and mood in humans (depression, anxiety, fear) through actions in the Bed Nucleus of the Stria Terminalis (BNST) and the Amygdala (AMY). Orexins also have inputs to brain regions important for arousal, such as the locus coeruleus (LC), which in turn can regulate activity in the limbic, thalamic and hypothalamic structure that are directly regulated by orexins.