Classically, the DMH and neurons in the surrounding PeF region have been recognized as key regulators of feeding behaviors, body weight regulation, neuroendocrine control, and metabolism (for a review, see Bellinger and Bernardis).
76 Further studies indicate that in addition to mobilizing sympathetic outflow in response to stress or threat, the DMH/PeF plays a critical role in regulating a wide range of behavioral, endocrine, and autonomic circadian rhythms.
29,77 For instance, the DMH/PeF region receives robust projections from the SCN,
29 and lesions to the DMH/PeF region disrupts the sleep-wake cycles
78 and circadian behaviors.
29 While there are many potential efferent pathways from the SCN that could control circadian fluctuation of IOP,
79–82 the DMH/PeF is a strong candidate since this region receives strong projections from the SCN, and plays a critical role in sympathetic mobilization and regulation of circadian activity (e.g., behavior, endocrine, and autonomic activity). This information, combined with our findings that chemical stimulation of the DMH/PeF evokes increases in IOP, provides compelling rationale for the hypothesis that the DMH/PeF is the putative location for hypothalamic control of IOP. Given the strong direct and indirect connections to the SCN
29 and extensive efferent connections to sympathetic autonomic relays and the endocrine system through the paraventricular nucleus,
36 we believe the DMH/PeF neurons are ideally situated to modulate the circadian fluctuations in IOP evoked by activity of SCN neurons and alterations in both ICP and the translaminar pressure gradient (see
Fig. 4). Future functional studies utilizing this microinjection model will help to determine whether this pathway alone or in concert with others contribute to circadian fluctuation of IOP and ICP.