The visual response properties of neurons in the nucleus of the basal optic root of the northern saw-whet owl (Aegolius acadicus).

The nucleus of the basal optic root (nBOR) in birds is a component of the accessory optic system (AOS) which is involved in the analysis of visual flowfields normally resulting from self-motion. Using standard extracellular techniques, we recorded from 81 single-unit and multi-unit clusters in the nBOR of the northern saw-whet owl, Aegolius acadicus, an avian species that has a visual system with frontal emphasis. These cells responded best to large patterns of random dots moving either upward (52%), downward (31%) or nasal to temporal (N-T; contralateral visual field; 15%). Only 2 units (2%) preferred temporal to nasal motion. 'Up' units were found in the dorsal portion of the nucleus whereas 'Down' units were located more ventrally. The N-T units were found in both the lateral margin of the nucleus and ventral to the Down units in the lateral half of the nucleus. About half of the units tested (10/19) responded to stimulation of the ipsilateral as well as the contralateral eye. For all but one cell, the direction preference of both eyes was the same in visual space. When compared with previous studies of pigeons (Columba livia) and chickens (Gallus domesticus), these findings reveal that the nBOR in all three avian species have important similarities with respect to direction preference and functional compartmentalization. Furthermore, the high proportion of binocular neurons found in the nBOR of the saw-whet owl is similar to the condition generally reported in frontal eyed mammals and hence may reflect adaptation.

Topography of short portal vessels in the rat pituitary gland: a scanning electron-microscopic and morphometric study of corrosion cast replicas.

We applied scanning electron microscopy combined with imaging and morphometric techniques to analyze the dorsal topography and morphology of short portal vessels linking the capillary beds of the pituitary neural and anterior lobes in adult male albino rats. The pituitary microvasculature was replicated by intracarotid injection of Batson's No. 17 compound producing plastic casts that were advantageous for comprehensive morphometric analyses using an imaging device. The analysis revealed the existence of two types of portal vessels having quantitatively different morphological properties. The bilateral venular plexus of 3-4 vessels located at the base of the infundibular stalk (each venule measuring 300 microns in length and 32 microns in diameter) appears to be the major part of the short portal system in the dorsum of the rat pituitary gland. Narrower capillary-like shunt vessels (6.8 microns in diameter), of about the same length as the venules, were situated throughout other subregions of the intermediate lobe cleft. The short portal vessels of both types made direct anastomoses with the capillary networks in the neural and anterior lobes. The neural lobe capillaries were twice as numerous (1324 per mm2), and only half as wide (6.2 microns), as the sinusoidal capillaries in the anterior lobe (density of 637 per mm2; diameter of 13.7 microns). The topographical position of the portal venular system suggests that the caudolateral subregions of the pituitary neural and anterior lobes have a functional relationship dependent on rapid interlobe transfer of neurohumoral factors such as hormones via the portal blood. This process appears to be supplemented throughout the rest of the cleft between the two lobes by a small number of capillary shunts that supply the epithelial cell lobules of the intermediate lobe in situ. The findings collectively indicate that this portal system provides a constant stream of neurohumoral information that is shared moment-by-moment between the pituitary neural and anterior lobes.

Metabolic and neuroanatomical correlates of barrel-rolling and oculoclonic convulsions induced by intraventricular endothelin-1: a novel peptidergic signaling mechanism in visuovestibular and oculomotor regulation?

The neuroactive peptide endothelin-1 has receptors distributed abundantly among subdivisions and nuclei of the visuovestibular and oculomotor systems. In previous work, we and others described the convulsive manifestations resulting from central injection of this neuropeptide, including nystagmus, oculoclonus, exophthalmos, tonic hindlimb extension, and a generalized repetitive motor disturbance called barrel-rolling. We applied the quantitative, autoradiographic [14C]deoxyglucose method to examine the hypothesis that visuovestibular and oculomotor structures would become metabolically stimulated when endothelin was introduced into the brain via the ventricular system in conscious rats. Since previous work had demonstrated that hypermetabolic responses to endothelin in other neural systems were inhibited by an antagonist of neuronal calcium L-type channels, nimodipine, we further tested whether the increased function of vestibulooculomotor nuclei whose metabolic activity was sensitive to endothelin could be altered following nimodipine pretreatment via the ventricle. A single unilateral injection of endothelin (9 pmol in 3 microliters saline) into a lateral ventricle provoked significantly increased rates of glucose metabolism in 22 of 39 individual anatomical structures of the visuovestibular and oculomotor systems. Among those affected were the superficial stratum of the caudal superior colliculus (+25%), the optic tract bilaterally (+35 to 43%), the oculomotor cranial nerve nuclei (III, IV, VI; range of +21 to 47%), and the medial terminal nucleus of the accessory optic tract which harbors dense fields of endothelin binding sites (bilateral increase of +70 to 96%). Several other nuclei involved in the proprioceptive and visuovestibular disturbance caused by endothelin displayed increased metabolic activity, including the cuneate, gracile, sensory trigeminal, and prepositus hypoglossal nuclei, the vestibular subnuclear system, and the cerebellar flocculus. Identification of hypermetabolic responsivity to endothelin in these structures provides further information on the anatomical substrates mediating the behavioral phenomenology of endothelin-induced motor convulsions which involve the paroxysmal participation of the extraocular muscles and motor control systems producing barrel-rolling convulsions. Nimodipine pretreatment inhibited both the convulsive activity and the cerebral hypermetabolic responses to intraventricular endothelin. The results indicate that the neural systems sensitive to intraventricular endothelin become functionally active via a calcium-mediated process that may involve the neuropeptide as an intrinsic signaling molecule.

Regional quantitative permeability of blood-brain barrier lesions in rats with chronic renal hypertension.

Blood-brain transfer constants for a small, neutral amino acid tracer, [14C]alpha-aminoisobutyric acid (AIB), were measured by quantitative autoradiography and image analysis in 15 individual brain structures of 2-kidney, 1-clip renal hypertensive rats (RHR) and age-matched normotensive controls (NR). Mean arterial pressures (MAP) for 4 month-old RHR and NR were 182 +/- 19 and 121 +/- 3 mmHg, respectively. Most brain structures in RHR had very low [14C]AIB transfer constants similar to those in NR (1-3 microliters.g-1.min-1), indicative of normal blood-brain barrier (BBB) function. Focal lesions, however, having transfer constants 2-7x normal and measuring less than 1.7 mm2 in area, appeared in RHR primarily in the cerebellar vermian and cerebral cortices. Chronic unilateral cervical sympathectomy did not influence the incidence or magnitude of BBB lesions in the denervated hemisphere of RHR. Acute arterial hypertension produced by systemic infusion of phenylephrine (elevation of MAP in RHR by 43%) increased the incidence and magnitude of lesions by 48% and 2-12x, respectively, although many brain regions in acutely hypertensive RHR retained normal permeability to [14C]AIB. The results demonstrate normal BBB permeability for much of the brain in chronic renal hypertension, with focal lesions having 7x or less the normal rate of blood-brain transfer for a small physiological probe.

Morphology and function of capillary networks in subregions of the rat tuber cinereum.

The differentiated cytology, cytochemistry, and functions within subdivisions of the tuber cinereum prompted this morphometric and physiological investigation of capillaries in the medium eminence and arcuate nucleus of albino rats. Morphometric studies established that the external zone of the median eminence had 3-5 times the number and surface area of true and sinusoidal capillaries than the internal or subependymal median eminence zones, or either of two subdivisions examined in the arcuate nucleus. Type-I true capillaries, around which Virchow-Robin spaces comprise 1% of arcuate tissue area, were situated proximally to the median eminence border. This finding is consistent with a premise that confluent pericapillary spaces enable infiltration of arcuate neurons by factors from capillary blood from the median eminence or Virchow-Robin spaces. Physiologically, the rate of penetration across the median eminence capillaries by blood-borne [14C]alpha-amino-isobutyric acid (a neutral amino acid used as a capillary permeability tracer) was 142 times greater than for capillaries in the distal arcuate nucleus within 12 s of tracer administration. A new finding was that the proximal arcuate nucleus had a permeability x surface area product of 69 microliters g-1 min-1, 34 times greater than that in more distal aspects of the tuber where blood-brain barrier properties exist. We also found that the microcirculatory transit time of a plasma space marker, [14C]sucrose, was considerably longer (1.2 s) in the median eminence and proximal arcuate nucleus than in the distal arcuate or ventromedial nucleus (0.4 s). By virtue of its high capillary permeability and extensive blood-tissue surface area, including the wide Virchow-Robin spaces, the median eminence external zone could be a gateway for flooding other tuberal compartments with blood-borne factors. This effect may be compounded by capillary bed specializations in the proximal arcuate nucleus where Type-I true capillaries, Type-III sinusoids, and pericapillary spaces are confluent with those in the median eminence. The results indicate that the proximal arcuate parenchyma could be exposed to circulating neuroactive substances on a moment-to-moment basis.

Subregional topography of capillaries in the dorsal vagal complex of rats: I. Morphometric properties.

Cytoarchitectonic and neurochemical studies of the dorsal vagal complex in the caudal medulla oblongata of rats indicate the existence of distinct anatomical and functional compartments within its components. We applied morphometric methods to discern whether capillary networks differed quantitatively between subregions and zones of area postrema, nucleus tractus solitarii (NTS), and dorsal motor nucleus of the vagus nerve (DMN) of rats. Analysis of 11 subdivisions of area postrema identified both "true" (range in luminal diameter of 3-7.5 microns) and sinusoidal (luminal diameter greater than 7.5 microns) capillaries that, together, made the capillary density for most of area postrema 75% greater than that found in NTS and DMN (526/mm2 vs about 300/mm2). The rank order of true capillary density in area postrema along its rostracaudal axis was caudal greater than central greater than rostral, whereas the reverse order was true for sinusoidal capillaries. Dorsal (periventricular) and medial zones of area postrema throughout its rostrocaudal axis tended to have higher values for capillary density, volume, surface area, luminal diameter, and pericapillary space volume than lateral or ventral zones bordering NTS. Within 200 microns of obex, the ventral zone of rostral area postrema was distinct, having a relatively sparse capillary density that may indicate morphological specializations limiting blood-tissue communication in this subregion. There were no quantitative differences in capillary dimensions between DMN and three subnuclei of NTS. These studies add to extant evidence that the dorsal vagal complex is differentiated for specific functions. Area postrema, especially, has topographical diversity in its capillary organization that likely corresponds to complex roles in neuroendocrine, autonomic, and chemosensory mechanisms.

Subregional topography of capillaries in the dorsal vagal complex of rats: II. Physiological properties.

The differentiated cytoarchitecture, neurochemistry, and capillary organization of the rat dorsal vagal complex prompted this comprehensive investigation of microvascular physiology in 11 subdivisions of area postrema, 5 subnuclei of nucleus tractus solitarii (NTS), the dorsal motor nucleus of the vagus nerve, and 4 other gray matter structures in the dorsal medulla oblongata. Microvascular exchangeable volume (residual plasma volume), capillary blood and plasma flow, and unidirectional transfer constants for a tracer amino acid, [14C]alpha-aminoisobutyric acid (AIB), varied considerably among the structures analyzed. Exchangeable volume, largest in area postrema medial zones (about 29 microliters.g-1) and smallest in medullary gray matter (7-11 microliters.g-1), correlated directly with subregional densities of capillaries and rates of tissue glucose metabolism. Capillary blood flow (range of 1,430-2,147 microliters.g-1.min-1), plasma flow, and tissue glucose metabolism (range of 0.48-0.71 mumol.g-1.min-1) were linearly related in the dorsal vagal complex. The most striking quantitative difference among structures in this brain region were the rates of transcapillary influx and derived permeability X surface area (PS) products of [14C]AIB, which has physicochemical properties resembling those of hormones. PS products for AIB were negligible in most medullary gray matter regions (less than 1 microliter.g-1.min-1, indicative of blood-brain barrier properties), but were 20-59X and 99-402X higher in NTS subnuclei and area postrema, respectively. An extraordinary feature of the microcirculation in area postrema was the long-duration transit of tracer sucrose and blood, a characteristic that would amplify the sensing ability of area postrema as it monitors the composition of the circulation.

Microvascular specializations promoting rapid interstitial solute dispersion in nucleus tractus solitarius.

Nucleus tractus solitarius (NTS), an aggregate of several individual nuclear groups in the dorsal medulla oblongata, is involved in virtually all autonomic functions as the first synaptic site in the brain for many peripheral viscerosomatic inputs. We found morphological evidence that dorsocaudal subregions of rat NTS (approximately 800 microns caudal from obex) had fenestrated capillaries and enlarged Virchow-Robin (perivascular) spaces that were similar to those in area postrema but unlike capillaries elsewhere in the medulla oblongata. Complexes of microvessels, consisting of up to 10 small vessels with smooth muscle layers (luminal diameters of 10-45 microns) and several capillaries (average luminal diameter of 4.5 microns), were located in the dorsal midline of NTS within large Virchow-Robin spaces measuring some 2,000 microns 2 in area. In physiological studies, we determined that most of NTS had a definable blood-brain barrier [permeability-surface area (PS) products for a neutral amino acid near 0], but medial and lateral aspects of the commissural subnucleus of NTS had PS products of 16-63 microliters.g-1.min-1 for alpha-[14C]aminoisobutyric acid 12 s after intravenous injection. Microvascular differentiations permitting such brisk tracer influx from blood resemble those of area postrema and appear to afford the rich neuropil of commissural NTS with a constant stream of blood-borne information for expediting its regulation of viscerosensory and autonomic functions.

Uncoupling of cerebral blood flow and glucose metabolism in conscious rats with chronic renal hypertension.

In an analysis of 46 individual brain structures and regions, we found that 12-14 weeks of renal hypertension in rats were associated with a 42% increase in cerebrovascular resistance, an average 28% reduction in cerebral blood flow, and no general change in cerebral glucose metabolism. A specific increase in metabolic activity, however, was identified in locus coeruleus. Generalized cerebral vasoconstriction resulting from central noradrenergic innervation originating in locus coeruleus is a possible explanation for the uncoupling of cerebral blood flow and metabolism in rats with chronic renal hypertension.

Focal metabolic effects of angiotensin and captopril on subregions of the rat subfornical organ.

Angiotensin infusion increased glucose metabolism in 4 of 7 subdivisions of the rat subfornical organ, the effect being stronger in ventromedial compared to dorsolateral zones across the rostrocaudal axis. [Sar1-Leu8]Angiotensin II attenuated metabolic responses to intravenous angiotensin in all subfornical organ subregions. Brattleboro rats, having high circulating levels of angiotensin, displayed greater rates of glucose metabolism than Long-Evans rats in all subregions, differences that were eliminated by captopril, an inhibitor of angiotensin converting enzyme. The studies reveal focal subfornical organ zones where in vivo metabolic activity corresponds to cytoarchitectonic evidence for topographical processing within this angiotensin-sensitive structure.

Quantitative fine structure of capillaries in subregions of the rat subfornical organ.

The differentiated cytology across subregions of the rat subfornical organ (SFO) prompted our hypothesis that ultrastructural features of capillary endothelial cells would vary topographically and quantitatively within this small nucleus. We used electron microscopic and computer-based morphometric methods to assess fine structural dimensions of the capillary endothelium in four distinct subregions of the SFO from Long-Evans and homozygous Brattleboro rats. Three types of capillary were present. Type III capillaries (resembling those of endocrine glands) had an average wall thickness of 0.17 microns, 54% thinner than those of Type I and II capillaries. Pericapillary spaces around Type III capillaries measured 56 microns2, 100% larger than for Type I vessels (resembling those of skeletal muscle). Only Type III capillaries contained fenestrations (9 per microns2 of endothelial cell) and were the predominant type of capillary in central and caudal subregions of the SFO. Type I capillaries, prevalent in the transitional subregion between the central and rostral parts of the SFO, had 10 cytoplasmic vesicles per micron2 of endothelial cell area, a number not different from that of Type III capillaries but 3x the frequency found in Type II vessels. Type II capillaries (those typical of "blood-brain barrier" endothelium) had low vesicular density (3 per microns2), no fenestrations, and no pericapillary spaces. Luminal diameters and the densities of mitochondria and intercellular junctions were not different among capillary types or subregions in the SFO. Furthermore, there were no morphometric differences for any capillary dimensions between Long-Evans and Brattleboro rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Metabolic activation of efferent pathways from the rat area postrema.

We used the quantitative [14C]deoxyglucose method and autoradiography to evaluate metabolic activity in 47 individual cerebral structures or subregions that are part of neural pathways emanating from the brain stem circumventricular organ, area postrema. Electrical stimulation of the dorsocentral area postrema in halothane-ventilated rats produced hypotension and increased glucose metabolism by several structures within the ascending trajectories of efferent neural projections from the nucleus. Structures in the caudal medulla oblongata, including three subnuclei of the nucleus of the solitary tract, dorsal motor nucleus of the vagus nerve, and nucleus ambiguus-A1 noradrenergic region, had increases of metabolism during stimulation of 32-62%. Pontine activation occurred specifically in the locus coeruleus and lateral parabrachial nuclei (increases of 24-36%). Magnocellular and parvocellular subdivisions of the hypothalamic paraventricular nucleus, supraoptic and suprachiasmatic nuclei, and median eminence showed increases in metabolism of 22-34%. An 89% elevation of glucose metabolism by the pituitary neural lobe resulted. The findings are evidence for functional activation of specific structures within ascending neural pathways from area postrema to forebrain mechanisms regulating blood pressure and fluid balance.

Differential rates of glucose metabolism across subregions of the subfornical organ in Brattleboro rats.

We applied [14C]deoxyglucose autoradiography and imaging techniques to determine rates of glucose metabolism in distinct subdivisions of the subfornical organ (SFO) of conscious Brattleboro rats. Seven anatomically-defineD SFO subregions were discerned having metabolic activities that differed from one another by as much as 29% in water-sated Brattleboro rats. The highest metabolic activity was found in the ventromedial zone of central and caudal subregions where previous studies identified the greatest densities of neurons, capillaries, putative angiotensin receptors, and angiotensin-immunoreactive fibers. Homozygous Brattleboro rats had rates of glucose metabolism that were 39-68% greater than those in corresponding SFO subregions of Long-Evans rats; these differences were accentuated by about 50% following 18 h of water deprivation. Exogenous treatment of Brattleboro rats with vasopressin uniformly normalized subregional glucose metabolism in the SFO. In Sprague-Dawley rats, water deprivation over 120 h provoked greater increases in metabolism of ventromedial than of dorsolateral SFO zones in amounts similar to the differences between Long-Evans and Brattleboro rats. The findings identify focal areas of high metabolic activity within subregions of the SFO where central responses are likely initiated to defend against homeostatic disturbances. The data represent further evidence for the probability that angiotensin II, as both hormone and neurotransmitter, is a metabolic stimulant of its target cells in the nervous system.

High metabolic activity in the dorsal vagal complex of Brattleboro rats.

Receptor densities for angiotensin II and atriopeptin are particularly high in the dorsal vagal complex (DVC) of the caudal medulla oblongata. Measurements of glucose metabolism in individual components of the DVC, compared with those in Long-Evans rats, revealed that the area postrema was activated selectively both in water-sated and water-deprived Brattleboro rats, which have high circulating levels of angiotensin II. Other parts of the DVC, including subnuclei of the nucleus of the solitary tract and the dorsal motor nucleus of the vagus nerve, as well as brainstem structures within efferent trajectories of the DVC, had elevated rates of glucose metabolism in Brattleboro rats deprived of water overnight and in Sprague-Dawley rats dehydrated for 120 h. The findings are consistent with neural activation by angiotensin II, as either a hormone or neurotransmitter, within subregions of the dorsal medulla oblongata having high densities of putative receptors and immunoreactive perikarya and fibers containing both angiotensin II and atriopeptin.