There are two distinct communication systems in the brain, term wiring and volume transmission (Agnati et al., 2010). Volume transmission refers to a way of communication lacking any wire-like channel connecting the source of signal and its target. This way of signaling is the focus of the current thesis. Portal systems are one aspect of volume transmission in which they provide a pathway for diffusible signaling between bodily fluids (blood and cerebrospinal fluid) and the nervous system. A portal system entails two capillary beds linked by connecting veins. This connection allows signals from one capillary bed to be transported to a target in high concentrations without being diluted in the systemic circulation (Dorland, 2020).
For the past decades, the only identified portal system in the brain is pituitary portal system (Popa, 1930; Popa & Fielding, 1933). Here, hypothalamic neurosecretions are released into the fenestrated capillaries of median eminence, a circumventricular organ, and transported to the capillaries of anterior pituitary via portal veins. The median eminence, due to its location on the surface of the ventricle and its contact to the cerebrospinal fluid, is categorized as a circumventricular organ. According to the classification (Oldfield & McKinley, 2015), there are three sensory circumventricular organs in the brain, all are characterized by fenestrated capillaries allowing contact between brain parenchyma and blood. For this reason, the circumventricular organs are known as “windows to the brain” (Gross et al., 1987). Whether other circumventricular organs also form portal systems is unknown. This thesis examines whether sensory circumventricular organs, specifically the organum vascular organ of the lamina terminals, the subfornical organ and the area postrema, bear portal systems. Although there have been prior studies of the vascularity of these CVOs in many species (reviewed in Duvernoy and Risold (2007)), the tissue preparation methods available limited the possibility of tracking small vessels over relatively large volumes in these structures.
In the present work, to preserve the blood vessel structure, brain clearing and light sheet microscopy were combined to acquire volumetric images of the regions containing the circumventricular organs. In vivo two-photon microscopy was used to study the blood flow of the sensory circumventricular organs and the adjacent neuropil. The results indicate that organum vasculosum of the lamina terminalis is connected to the brain’s clock located in the suprachiasmatic nucleus by portal vessels. The direction of blood flow is from the suprachiasmatic nucleus to the organum vasculosum of the lamina terminalis, and speed of blood flow is faster during the night compared to the day. Volumetric imaging of the suprachiasmatic nucleus also shows portal veins emerging from the rostral shell region of this nucleus. Also, the subfornical organ connects to the septofimbrial nucleus and the triangular nucleus of the septum via portal veins.
The arrangement of the vasculature of the area postrema differs from the other sensory CVOs: the AP and the nucleus of the solitary tract share a common capillary bed directly joining the vasculature of these morphologically distinct nuclei. In summary, there are multiple portal systems connecting the circumventricular organs. These newly discovered portal systems represent new pathways for diffusible signaling, bridging the systemic circulation, cerebrospinal fluid, circumventricular organs and the portal veins connected regions.
| Identifer | oai:union.ndltd.org:columbia.edu/oai:academiccommons.columbia.edu:10.7916/k1yx-da09 |
| Date | January 2023 |
| Creators | Yao, Yifan |
| Source Sets | Columbia University |
| Language | English |
| Detected Language | English |
| Type | Theses |
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