Fig. 12.13 Figure 1 redrawn from Steinle et al. [322] showing a laser Doppler blood ßow record from the anterior choroid, posterior choroid, and vortex veins of rats during stimulation of either the SSN or the cervical sympathetic trunk (CST). The bar indicates the duration of the SSN (20 Hz) or the CST (12-Hz stimulation). Note that the CST stimulation decreased ChBF in posterior choroid, while SSN stimulation increased ßow in the anterior choroid and vortex veins

Flux (arbitrary units)

150

100

50

0

anterior choroid, SSN vortex veins, SSN posterior choroid, SSN posterior choroid, CST

also appear to be cholinergic [63, 354] and muscarinic agonists yield choroidal vasodilation [114, 218].

12.5.3.4 Choroidal Autoregulation and the PPG Input to Choroid – Mammals

The issue of choroidal autoregulation (i.e., compensation for ocular perfusion pressure changes so as to maintain ChBF near basal levels) has been somewhat controversial, since earlier studies reported that ChBF decreased linearly with reductions in choroidal perfusion pressure caused by acute hemorrhage or increased IOP [4, 10, 33, 37]. These observations had, in fact, led to a dogma that while cerebral blood ßow and retinal blood ßow do autoregulate to maintain stale ßow despite reduced ocular perfusion pressure, choroidal blood ßow does not. It became increasingly evident from subsequent studies, however, that ChBF does compensate for perfusion pressure declines. For example, some autoregulation with IOP elevations was noted in cats [97, 390], rabbits [54], and humans [292]. Detailed studies in rabbits have shown that when ocular perfusion pressure is experimentally reduced by lowering BP rather than by raising IOP, stable ChBF over a blood pressure (BP) range of 40Ð50 below basal BP is observed [169]. The compensation was hypothesized to stem from myogenic mechanisms [171]. In a later study, Kiel [173] noted that both NOS inhi-

bition and ganglionic blockade diminished the ChBF compensation to systemic hypotension in rabbit, implying some involvement of neurogenic vasodilatory mechanisms in the compensation. We refer to the blood ßow compensation for reduced systemic BP as baroregulation. By contrast, Jacot et al. [156] showed in piglet that ChBF compensation to perfusion pressure changes caused by IOP manipulation do not involve NO release, and thus involve different mechanisms that are involved in choroidal baroregulation. It is now evident than it is unlikely that ChBF would not show compensation for reduced ocular perfusion pressure, given the potentially adverse consequences of either supranormal ChBF or subnormal ChBF on retinal health and function. Without autoregulation, high BP would yield an ocular perfusion pressure resulting in excessively high ChBF, causing ßuid accumulation in retina and deÞcient exchange of wastes and nutrients between retina and choroid [35, 170]. Similarly, without autoregulation, low BP would yield an ocular perfusion pressure resulting in low ChBF, causing retinal hypoxia and impaired retinal function [325, 399, 400].

Given the input of hypothalamic and solitary nucleus blood pressure-sensitive sites to the choroidal neurons of the SSN [65, 147, 154, 323], at least part of the choroidal compensation to BP declines may be mediated by the SSN-PPG

circuit. Consistent with this possibility, prior studies have suggested that at least part of the compensation of cerebral blood ßow for declines in BP may be mediated by the PPG [121, 245]. Moreover, systemic hypotension does not activate sympathetic input to the choroid, while it does cause peripheral vasoconstriction [34]. Thus, the eye (like the brain) is a privileged tissue during systemic hypotension. Nonetheless, Linder [203] found that facial nerve stimulation increased choroidal blood ßow in hypotensive rabbit, but facial nerve section did not reduce choroidal blood ßow in hypotensive or normotensive rabbit, suggesting little contribution of the facial nerve system to hypotensive or normotensive tone in anesthetized rabbit. These results argue against the notion that the SSN-PPG circuit to the choroid participates in ChBF compensation for low systemic blood pressure, at least in rabbits. Given the anatomical evidence for BP-sensitive inputs to the SSN, however, further studies are needed to assess the contribution of the SSN-PPG circuit in mammals to ChBF baroregulation.

Note that the choroidal circulation does not appear to regulate (decrease) to high oxygen levels but does regulate (increase) in response to high CO2. For example, ChBF is unaltered in response to breathing 100% oxygen in humans [112, 167, 291] but is increased by breathing carbogen (95% O2 Ð 5% CO2) [112]. Similarly, hypercarbia increases ChBF in newborn piglets, cats, sheep, and baboons [5, 238, 332, 395]. High CO2 is also known to increase cerebral blood ßow as well [395]. The mechanism of the increased blood ßow with hypercapnia is uncertain. Schmetterer et al. [305] reported that NO is involved in hypercapnia-mediated increases in blood ßow in the human ophthalmic artery, raising the possibility that the same is true for the choroid. Cyclooxygenase products do not appear to mediate the hypercapnic ChBF increase in newborn piglets [331]. Note that some newborn mammals such as piglets [333] but not sheep [243] show a ChBF decrease to breathing 100% O2 Ð the increase in piglets also does not appear to be mediated by cyclooxygenase products. Whether vasodilatory PPG input plays a role in hypercapnic ChBF increases is unknown.

12.5.3.5Peripheral Anatomy of Facial Circuitry for Control

of ChBF – Birds

The pigeon PPG consists of an interconnected series of three to four microganglia of about 50Ð200 neurons each and numerous lesser microganglia (Figs. 12.14 and 12.15) [63]. The main microganglia of the PPG network in pigeons lie along the superior aspect of the Harderian gland. Neurons of all of these microganglia are extremely rich in VIP and nNOS, and moderate in ChAT (and thus make acetylcholine), and the majority co-contain VIP and nNOS (Fig. 12.16). In pigeons and chickens, the PPG has been shown to innervate choroidal vessels, as well as orbital vessels supplying the choroid [63, 85]. Axons containing VIP and nNOS extend from the PPG network to perivascular Þber plexi on orbital blood vessels [63]. These orbital vessels, many of which enter the choroid posteriorly and nasally, are a conduit by which PPG postganglionic Þbers reach the choroid (Fig. 12.15). Within the choroid, VIP+ and nNOS+ Þbers are widely scattered but sparse, and most abundant in nasal choroid. These results suggest that PPG neurons in birds use VIP and NO, and also possibly acetylcholine, to exert vasodilatory control over blood ßow to and within the avian choroid. A few VIP+ and nNOS+ neurons were also observed in the choroid. In some avian groups, such as ducks, many more intrinsic choroidal neurons co-containing VIP and nNOS have been reported [26, 306, 307, 309], as described here in more detail in a later section.

12.5.3.6Central Anatomy of Facial Circuitry for Control

of ChBF – Birds

Several studies have suggested that the preganglionic neurons innervating the PPG in birds reside in the superior salivatory nucleus in a similar brainstem location as in mammals [108, 228, 310]. Schroedl et al. [310] recently carried out a detailed anatomical study on the localization of the avian SSN (Fig. 12.17). ChAT+ neurons in brainstem were retrogradely labeled via the radix autonomica of the facial nerve, which conveys preganglionic axons from the SSN to the PPG. The SSN neurons were located dorsolateral to somatic facial

Fig. 12.14 Schematic illustrations of the major ocular nerves (a) and vessels (b) and their relationship to the Harderian gland in birds, both as viewed from the posterior aspect of the left eye. Schematic (a) shows the course and relative locations of several major orbital nerves, as well as the locations of the ciliary ganglion (CG) and a simpliÞed version of the PPG system of microganglia. A more detailed version of the PPG is shown in Fig. 12.15. Schematic (b) illustrates the origin of the ophthalmotemporal artery from the external ophthalmic artery (which is itself a branch of the internal carotid) and its orbital course

along the left eye. Note the course of the ophthalmotemporal artery along the temporal, posterior, and nasal poles of the eye, and note that it gives rise to choroidal arteries throughout its course. It also gives rise to additional muscular and glandular branches. The ophthalmotemporal artery is accompanied by a vein of the same name whose major branches are somewhat different from those of the artery. Superior is to the top and nasal to the right in both schematics. inf inferior branch of oculomotor nerve, OPH ophthalmic nerve, sup superior branch of oculomotor nerve

motoneurons, as they are in mammals. As in mammals, the SSN region receives input from the nucleus of the solitary tract [14], the parabrachial region [394], and the SSN [180]. As in mammals,

the parabrachial region receives input from the nucleus of the solitary tract, which receives baroreceptive input [28, 164]. Thus, as in mammals, the avian SSN-PPG circuit may be responsive to

Fig. 12.15 Image (a) provides a schematic view of the left Harderian gland and associated PPG plexus, as seen from the nasal side (i.e., the side facing the orbit). The ophthalmic nerve (OPH) is shown as coursing superior to the gland and receiving Þbers from the PPG plexus. The nasal branch of the ophthalmotemporal artery is shown behind the gland. The two major PPG microganglia are located along the superior aspect of the Harderian gland and are indicated by

arrows. The more rostral of these two is typically referred to as Òthe PPGÓ in many previous published works. NADPH-diaphorase neurons within the various microganglia are shown as solid circles. Image (b) provides a superior view of the Harderian gland and the ophthalmotemporal artery between it and the eye. Nerve Þbers on the artery and its branches to the choroid are illustrated

baroreceptor information and thus regulate ChBF as a function of systemic blood pressure.

12.5.3.7Physiological Studies of Facial Parasympathetic Control

of ChBF – Bird

In unpublished studies, we used transcleral LDF to measure ChBF in pigeons while systematically electrically stimulating brainstem in the vicinity of the facial motor nucleus, focusing on the region

of small cholinergic neurons between the two motoneuron pools comprising the SSN in chickens that had been shown to project to the PPG [108, 310]. We found that the region of the SSN of birds was effective for eliciting ChBF increases (100% or more) without signiÞcant concomitant systemic BP increases. The NOS inhibitor 7-nitroindazole (7NI) greatly attenuated (about 50%) the ChBF increases that could be elicited from this region, consistent with an involvement

Fig. 12.16 Photomicrographs of immunolabeling in the main ganglion making up the avian PPG network. Images (aÐc) show three adjacent sections of the main PPG, labeled for VIP (a), NADPHd (b), and ChAT (c). The ganglion is rich in VIP+ and NADPHd+ perikarya, but poorer in ChAT perikarya. The ChAT perikarya are embedded within the ChAT+ neuropil of this PPG microganglion. The axon bundle shown to the extreme left in each photomicrograph contains VIP+, NADPHd+, and ChAT+ axons. The Harderian gland (HG) is shown to the upper left in all three photomicrographs. Images (dÐg) show single Þelds of view of the main PPG microganglion

in frontal sections, double-labeled by immunoßuorescence for VIP and nNOS. As can be seen in image pair (d and e), and a higher-power view of part of the same Þeld (f and g), numerous individual perikarya in the gland are labeled for VIP and nNOS. The large arrows in (d and e) indicate three such double-labeled neurons, and these same neurons are indicated in (f and g) by large arrows. In addition, a number of other neurons labeled for both VIP and nNOS are indicated in (f and g) by small arrows. MagniÞcation the same in (aÐc). MagniÞcation the same in (d and e). MagniÞcation the same in (f and g)

Fig. 12.17 Schematic images from Fig. 9 of Schrodl et al. [310]. The schematics show a mapping of the right side of the brainstem in a rostral (a) to caudal (b) pair of transverse sections. Preganglionic parasympathetic neurons of the SSN, as identiÞed by retrograde tracing, are indicated by open triangles. Black dots represent motoneu-

rons of somatic facial motor nucleus nerve VII. Cb cerebellum, Flm fasciculus longitudinalis medialis, L lingula, MCC nucleus magnocellularis cochlearis, nVI nucleus abducens, NVI nervus abducens, NVIII nervus vestibulocochlearis, OS nucleus olivaris, V4 fourth ventricle, Vem nucleus vestibularis medialis, R raphe nucleus