Cortical cyto- and chemoarchitecture in three small Australian marsupial carnivores: Sminthopsis macroura, Antechinus stuartii and Phascogale calura.

The cyto- and chemoarchitecture of the cerebral cortex has been examined in three small (mouse-sized) polyprotodont marsupial carnivores from Australia (the stripe-faced dunnart, Sminthopsis macroura; the brown antechinus, Antechinus stuartii; and the red-tailed phascogale, Phascogale calura) in order to compare the cortical topography of these marsupials with that of diprotodontids, didelphids and eutherians. All three species studied had similar cortical cytoarchitecture. The isocortical surface was dominated by primary somatosensory (S1) and visual (V1) areas. Putative secondary sensory areas (S2, V2M, V2L) were also identified. The primary somatosensory cortex demonstrated clumps of granule cells in the presumptive mystacial field, whereas the primary visual area showed a distinctive chemical signature of intense calbindin immunoreactivity in layer IV. On the other hand, the primary auditory area was small and indistinct, but flanked by a temporal association area (TeA). A cytoarchitecturally distinct primary motor cortex (M1) with prominent pyramidal neurons in layer V and poor layer IV was identified medially to S1, and at rostral levels a putative secondary motor area was identified medial to M1. Transitional areas between isocortex and allocortical regions showed many cyto- and chemoarchitectural similarities to those reported for eutherian (and in particular rodent) cortex. Medially, two cingulate regions were found at rostral levels, with dysgranular and granular 'retrosplenial' areas identified caudally. Laterally, granular and agranular areas surrounded the rostral rhinal fissure, to be replaced by ectorhinal and perirhinal areas caudally. The findings indicate that the cyto- and chemoarchitectural features which characterize the iso- and allocortex in these small marsupial carnivores are similar to those reported in didelphids and eutherians and our findings suggest the existence of putative dedicated motor areas medial to the S1 field.

Development of the human dorsal nucleus of the vagus.

The dorsal nucleus of the vagus nerve plays an integral part in the control of visceral function. The aim of the present study was to correlate structural and chemical changes in the developing nucleus with available data concerning functional maturation of human viscera and reflexes. The fetal development (ages 9 to 26 weeks) of the human dorsal nucleus of the vagus nerve has been examined with the aid of Nissl staining and immunocytochemistry for calbindin and tyrosine hydroxylase. By 13 weeks, the dorsal vagal nucleus emerges as a distinct structure with at least two subnuclei visible in Nissl stained preparations. By 15 weeks, three subnuclei (dorsal intermediate, centrointermediate and ventrointermediate) were clearly discernible at the open medulla level with caudal and caudointermediate subnuclei visible at the level of the area postrema. All subnuclei known to exist in the adult were visible by 21 weeks and cytoarchitectonic differentiation of the nucleus was largely completed by 25 weeks. The adult distribution pattern of calbindin and tyrosine hydroxylase immunoreactive neurons was also largely completed by 21 weeks, although morphological differentiation of labeled neurons continued until the last age examined (26 weeks). The structural development of the dorsal nucleus of the vagus nerve appears to occur in parallel with functional maturation of the cardiovascular and gastric movements, which the nucleus controls.

Cyto- and chemoarchitecture of the cerebellum of the short-beaked echidna (Tachyglossus aculeatus).

The monotremes (echidnas and platypus) have been claimed by some authors to show 'avian' or 'reptilian' features in the gross morphology and microscopic anatomy of the cerebellum. We have used Nissl staining in conjunction with enzyme histochemistry to acetylcholinesterase and cytochrome oxidase and immunohistochemistry to non-phosphorylated neurofilament protein (SMI-32 antibody), calcium binding proteins (parvalbumin, calbindin and calretinin) and tyrosine hydroxylase to examine the cyto- and chemoarchitecture of the cerebellar cortex and deep cerebellar nuclei in the short-beaked echidna. Immunoreactivity for non-phosphorylated neurofilament (SMI-32 antibody) was found in the deep cerebellar nuclei and in Purkinje cells of most regions except the nodule. Purkinje cells identified with SMI-32 immunoreactivity were clearly mammalian in morphology. Parvalbumin and calbindin immunoreactivity was found in Purkinje cells with some regional variation in staining intensity and in Purkinje cell axons traversing cerebellar white matter or terminating on Lugaro cells. Calbindin immunoreactivity was also present in inferior olivary complex neurons. Calretinin immunoreactivity was found in pontocerebellar fibers and small cells in the deep granule cell layer of the ansiform lobule. We found that, although the deep cerebellar nuclei were much less clearly demarcated than in the rodent cerebellum, it was possible to distinguish medial, interposed and lateral nuclear components in the echidna. As far as we can determine from our techniques, the cerebellum of the echidna shows all the gross and cytological features familiar from the cerebellum of therian mammals.

Development of the human nucleus of the solitary tract: a cyto- and chemoarchitectural study.

The present study investigated the prenatal development of the cyto- and chemoarchitecture of the human nucleus of the solitary tract from 9 to 35 weeks, by using Nissl staining and immunoreactivity to calbindin, calretinin, tyrosine hydroxylase and GAP-43. The nucleus began to gain heterogeneity and show different subnuclei as early as 13 weeks, and approached cytoarchitectural maturation from 21 to 25 weeks. The subnuclear division pattern observed in the fetal nucleus of the solitary tract at 25 weeks was very similar to that of the adult. Neurons immunoreactive to calbindin first appeared in the medial gastrointestinal area of the nucleus at 13 weeks, particularly within a putative gelatinosus subnucleus, while calretinin immunoreactivity during fetal life suggested the possible presence of a central subnucleus. Tyrosine hydroxylase immunoreactive neurons were seen in the medial subdivisions of the nucleus of the solitary tract as early as 13 weeks, but the population continued to increase until 25 weeks. Strong GAP-43 immunoreactivity was also present in the nucleus of the solitary tract at 13 weeks, especially in the dorsolateral and commissural subnuclei, while at 21 weeks there was a significant decline of GAP-43 expression. Results from the chemoarchitectural study showed that the human nucleus of the solitary tract expressed various neurochemical substances at an early developmental age (13 weeks), even before cellular and neuropil maturation was fully attained. Expression of these factors may play an important role in establishment and integration of viscerosensory function in the nucleus.

The brain angiotensin system: insights from mapping its components.

Mapping of components of the angiotensin (Ang) system in the brain suggests that it serves multiple central roles, including regulation of fluid and electrolyte balance, central autonomic control, and pituitary hormone release.

Termination of vestibulospinal fibers arising from the spinal vestibular nucleus in the mouse spinal cord.

The present study investigated the vestibulospinal system which originates from the spinal vestibular nucleus (SpVe) with both retrograde and anterograde tracer injections. We found that fluoro-gold (FG) labeled neurons were found bilaterally with a contralateral predominance after FG injections into the upper lumbar cord. Anterogradely labeled fibers from the rostral SpVe traveled in the medial part of the ventral funiculus ipsilaterally and the dorsolateral funiculus bilaterally in the cervical cord. They mainly terminated in laminae 5-8, and 10 of the ipsilateral spinal cord. The contralateral side had fewer fibers and they were found in laminae 6-8, and 10. In the thoracic cord, fibers were also found to terminate in bilateral intermediolateral columns. In the lumbar and lower cord, fibers were mainly found in the dorsolateral funiculus bilaterally and they terminated predominantly in laminae 3-7 contralaterally. Anterogradely labeled fibers from the caudal SpVe did not travel in the medial part of the ventral funiculus but in the dorsolateral funiculus bilaterally. They mainly terminated in laminae 3-8 and 10 contralaterally. The present study is the first to describe the termination of vestibulospinal fibers arising from the SpVe in the spinal cord. It will lay the anatomical foundation for those who investigate the physiological role of vestibulospinal fibers and potentially target these fibers during rehabilitation after stroke, spinal cord injury, or vestibular organ injury.

Aging-dependent changes in the cellular composition of the mouse brain and spinal cord.

Although the impact of aging on the function of the central nervous system is known, only a limited amount of information is available about accompanying changes affecting the cellular composition of the brain and spinal cord. In the present work we used the isotropic fractionator method to reveal aging-associated changes in the numbers of neuronal and non-neuronal cells harbored by the brain and spinal cord. The experiments were performed on 15-week, 7-month, 13-month, and 25-month-old female mice. The major parts of the brain were studied separately, including the isocortex, hippocampus, cerebellum, olfactory bulb, and the remaining part (i.e., 'rest of brain'). The proliferative capacity of each structure was assessed by counting the number of Ki-67-positive cells. We found no aging-dependent change when the cellular composition of the isocortex was studied. In contrast, the neuronal and non-neuronal cell numbers of the hippocampus decreased in the 7-25-month period. The neuronal cell number of the olfactory bulb showed positive age-dependence between 15 weeks and 13 months of age and presented a significant decrease thereafter. The cerebellum was characterized by an age-dependent decrease of its neuronal cell number and density. In the rest of brain, the non-neuronal cell number increased with age. The neuronal and non-neuronal cell numbers of the spinal cord increased, whereas its neuronal and non-neuronal densities decreased with age. The number of proliferating cells showed a marked age-dependent decrease in the hippocampus, olfactory bulb, and rest of the brain. In contrast, the number of Ki-67-positive cells increased with age in both the cerebellum and spinal cord. In conclusion, aging-dependent changes affecting the cellular composition of the mouse central nervous system are present but they are diverse and region-specific.

Angiotensin II receptors and angiotensin converting enzyme in the medulla oblongata.

Quantitative in vitro autoradiography was used to map angiotensin II (ANG II) receptors and angiotensin converting enzyme (ACE) in sections from rat, rabbit, sheep, and human medulla oblongata and to follow changes in receptor and ACE density after disruption of vagal projections by nodose ganglionectomy in the rat. ANG II receptors and ACE are both concentrated in the nucleus of the solitary tract and dorsal motor nucleus of vagus of the rat, rabbit, sheep, and human. An ANG II receptor-containing band connecting the nucleus of the solitary tract with the dorsolateral medulla was seen in rabbit and human tissue, providing evidence for association of ANG II receptors with vagal afferent fibers. ANG II receptors were found to be concentrated in the rostral and caudal ventrolateral medulla, which corresponded to the region of C1 and A1 catecholamine-containing cell groups in the rabbit. This localization was also evident in rat and human tissue. In all four species, a prominent, ANG II receptor-rich band in the intermediate reticular nucleus was found to connect the ventrolateral medulla and the dorsal vagal complex. In humans and sheep, this band contains puncta that overlie cell bodies. One week after nodose ganglionectomy in the rat, the density of ANG II receptors in the ipsilateral dorsal vagal complex fell markedly. This fall was most prominent in the rostral dorsal motor nucleus of vagus (to 46% of control density) and in the nucleus of the solitary tract (to 56% of control). ACE levels and calcitonin gene-related peptide receptor density were unchanged in both nuclei after ganglionectomy.(ABSTRACT TRUNCATED AT 250 WORDS)

Evidence for plasticity of the dopaminergic system in parkinsonism.

A series of compensatory mechanisms within the dopaminergic system have been shown to maintain clinical function in the presence of dopamine loss. Experimental evidence for increased presynaptic dopamine turnover owing to increased dopamine synthesis, release, and reduced reuptake exists. Direct evidence that these mechanisms maintain extracellular dopamine levels is provided by intracerebral microdialysis techniques. Postsynaptic denervation supersensitivity clearly occurs with D2 dopamine receptors, although this is less evident with D1 receptors. Similarly, mechanisms of plasticity have been shown to be relevant in human postmortem and Positron Emission Tomographic studies of patients with Parkinson's disease. However, although presynaptic increases in dopamine turnover are well documented, postsynaptic D1 and D2 receptor changes have been more difficult to establish, mainly because of methodological difficulties. D2, but not D1, receptor increases have been documented in drug naive Parkinsonian patients with PET techniques. In transplantation of adrenal gland to striatum in animal models and patients with Parkinsonism where clinical improvement occurs, plasticity of host response may be as important as plasticity of the graft. Although some elements of the compensatory mechanism of dopamine plasticity may be deleterious, such as dyskinesias owing to dopamine receptor supersensitivity, the overall effect of delay and minimization of the clinical expression of disease is advantageous. An even greater understanding of the mechanisms involved may assist in developing future therapeutic strategies.

Architectonic analysis of the human retrosplenial cortex.

The architecture of the macaque retrosplenial cortex, including its posteroventral extension around and below the splenium of the corpus callosum, was recently characterized (Morris et al. [1999a] Eur. J. Neurosci. 11:2506-2518.). This analysis was made possible by sectioning the posterior cingulate gyrus radially, i.e., in planes that were orthogonal to its line of curvature and that, therefore, preserved the laminar organization of this region. The aim of the present study was to examine the architecture and the limits of the human retrosplenial cortex. Cross sections through the entire posterior cingulate gyrus were obtained by applying the sectioning technique developed in the monkey, so that an explicit comparison could be made between the architecture of the human and the monkey retrosplenial cortex. The present analysis revealed that, as is the case in the macaque brain, the human retrosplenial cortex is composed of granular areas 29a-c and d, and dysgranular/agranular area 30. The human retrosplenial cortex, like that of the macaque monkey, runs, as an arch, around the splenium of the corpus callosum. In the macaque brain, the retrosplenial cortex remains buried within the callosal sulcus throughout its entire course around the splenium. In the human brain, however, the posteroventral segment of the retrosplenial cortex extends on the medial wall of the cerebral hemisphere to encompass most of the cortical region commonly referred to as the "isthmus of the cingulate gyrus."

Human intermediate reticular zone: a cyto- and chemoarchitectonic study.

The primary aim of this study was to provide a comprehensive account of the morphology, topography, and frequency of tyrosine hydroxylase- and substance P-like (TH-LI, SP-LI) immunoreactive neurons of the human intermediate reticular zone (IRt), the putative autonomic zone of the medullary reticular formation. A further aim is to examine the IRt from a three-dimensional perspective using computer reconstruction techniques and compare its relationship with other structures in the rest of the medullary reticular formation. Six adult human brains were obtained from individuals with no sign of cerebral disease and were perfusion fixed. Free-floating transverse sections were immunostained with monoclonal antibodies against tyrosine hydroxylase and substance P by the avidin-biotin-peroxidase technique. The entire IRt displays TH-LI cell bodies and fibers, and thus it is readily distinguishable from the neighbouring gigantocellular and parvicellular reticular nuclei. In contrast, SP-LI cells are restricted to the external part of the IRt that is found in the open medulla, while SP-LI fibers are more widely distributed. The IRt displays TH-LI neurons which are fusiform, oval, and round in shape. The SP-LI neurons of the IRt are primarily oval and fusiform. In preparations stained for Nissl substance, IRt cells were classified as pigmented and nonpigmented. A characteristic feature of the IRt is that its cells are larger (20 +/- 4 micrograms) than those of the laterally adjoining parvicellular (12 +/- 2 micrograms) and clearly smaller than those of the medially adjoining gigantocellular nuclei (33 +/- 6 micrograms). The shape of the IRt is in keeping with the radial organization of the medulla with zones emanating from the fourth ventricle. Three-dimensional computer reconstructions of the cell plots show that 1) TH-LI neurons extend through the entire IRt and densely packed in the rostral part of the ventrolateral IRt and 2) SP-LI neurons are found only in the rostral half of the medulla oblongata.

Dorsal motor nucleus of the vagus nerve: a cyto- and chemoarchitectonic study in the human.

In order to investigate the topography and subdivisions of the human dorsal motor nucleus of the vagus nerve (10), studies were conducted using cyto- and chemoarchitectonic (acetylcholinesterase and substance P-like immunoreactivity) and computer reconstruction techniques. The six brainstems examined were obtained within 17 hours postmortem from adults with no known neurological disorders. Serial sections cut in transverse, sagittal, and coronal planes were stained with cresyl violet, or tested for acetylcholinesterase or substance P. The neurons of the 10 (16,826 +/- 967) displayed cyto- and chemoarchitectonic heterogeneity and could be classified into six types. Types I-V consist of presumed vagal motor neurons (13,802 +/- 844), while the remaining type (Type VI) consisted of presumed interneurons (3,024 +/- 769). The 10 was subdivided into nine subnuclei grouped regionally into rostral, intermediate, and caudal divisions on the basis of neuronal morphology, cell density, and differential AChE and substance P reactivities. The rostral division contains the dorsorostral (DoR) and the ventrorostral (VeR) subnuclei; the intermediate division contains the rostrointermediate (RoI), dorsointermediate (DoI), centrointermediate (CeI), ventrointermediate (VeI), and caudointermediate (CaI) subnuclei; the caudal division (Ca) is not subdivided. Morphologically, small round or oval cells populate the VeR and VeI. Medium-sized oval cells occur in the DoR, CeI, and Ca, while medium-sized fusiform and multipolar cells are the main features of CaI. Large triangular cells appear mainly in DoI. Glial cells show the highest predilection for CeI, lowest densities in DoI and medial fringe subnucleus (MeF), and intermediate densities in the remaining six subnuclei. VeI showed the strongest AChE reactivity. Although the cell bodies of VeR and DoI are AChE positive, the neuropil (background) is weakly stained. Densely distributed fine granular substance P-like immunoreactivity occurs throughout the entire nucleus, while the intermediate and caudal divisions contain substance P-like-immunoreactive neurons. Three-dimensional computer reconstructions afforded an appreciation of the distinctiveness of the intermediate division (a division that contains the majority of cells) and the caudal division, which displays the lowest density of presumed vagal motoneurons. It is possible that the subnuclei identified herein form functional units innervating specific organs.

In vitro autoradiographic localization of calcitonin binding sites in human medulla oblongata.

In this study we examined the distribution of calcitonin (CT) binding sites in the human medulla oblongata by in vitro autoradiography. In competition studies, the rank order of potency for calcitonins competing for 125I-salmon CT binding was salmon CT > porcine CT > human CT, which is consistent with physiologically relevant CT receptors in other systems. For the determination of CT binding in the human medulla, 20-micron cryostat sections were incubated with 125I-salmon CT in the presence or absence of 10(-6) M unlabelled salmon CT to map specific CT binding sites. Punctate binding was observed over discrete nuclei of the medulla. High binding densities were seen over subnuclei of the dorsal motor nucleus of the vagus, the nucleus of the solitary tract, the intermediate reticular zone, the gigantocellular and dorsal paragigantocellular nuclei, and the raphe obscurus nucleus. Moderate levels of binding were observed over the lateral paragigantocellular nucleus and the rostral extent of the epiolivary nucleus. The cuneate and gracile nuclei and the fiber tracts did not contain detectable binding, while the inferior olivary nucleus had moderate levels of nonspecific binding. The localization of calcitonin binding sites in the human presents similarities but also important differences to the distribution in rat and cat. The most notable difference is the extreme binding densities in the intermediate reticular zone of the human. The location of binding sites suggests involvement of calcitonin in regulation of autonomic function.

The dorsal, posterodorsal, and ventral tegmental nuclei: a cyto- and chemoarchitectonic study in the human.

In order to verify the existence of the ventral and posterodorsal tegmental nuclei and to extend previous findings regarding the dorsal tegmental nucleus in the human brainstem, studies were conducted using cyto- and chemoarchitectonics, and computer reconstruction techniques. Serial sections of five brainstems from adults with no known neurological disorders were stained for Nissl substance, acetylcholinesterase, and substance P. The topography, cytoarchitecture, and acetylcholinesterase reactivity of the tegmental nuclei were presented in a mini-atlas depicting sections cut in transverse and sagittal planes. The dorsal and posterodorsal tegmental nuclei were identified fully within the central grey matter while the ventral tegmental nucleus extended across the medial longitudinal fasciculus into the pontine reticular formation. The dorsal tegmental nucleus featured a cell-poor pericentral part, strongly positive for acetylcholinesterase, and a central part comprised of densely packed small neurons that displayed moderate acetylcholinesterase reactivity and strong substance P-like immunoreactivity. The posterodorsal tegmental nucleus, located in the same transverse plane as the rostral part of the motor nucleus of the trigeminal nerve, was composed of diffusely arranged small to medium neurons with its neuropil displaying moderate acetylcholinesterase reactivity and strong substance P-like immunoreactivity. The ventral tegmental nucleus, identified as a prominent structure in the pontine tegmentum immediately rostral to the genu of the facial nerve, contained predominantly large neurons and displayed intensive acetylcholinesterase reactivity and substance P-like immunoreactivity. These studies showed that the tegmental nuclei, which displayed distinctive cyto- and chemoarchitectonic features, were fully present in adult human brainstem.

Substance P- and tyrosine hydroxylase-containing neurons in the human dorsal motor nucleus of the vagus nerve.

The aim of this study was to provide a comprehensive account of the topography, morphology, and frequencies of the substance P- and tyrosine hydroxylase-containing neurons in the human dorsal motor nucleus of the vagus nerve. The morphology of immunoreactive neurons was studied and the variations of the cell distributions were presented by three-dimensional computer reconstructions. Three types of substance P-like immunoreactive neurons were identified. They were predominantly located in the dorsointermediate, centrointermediate, caudointermediate, and caudal division of the dorsal motor nucleus of the vagus nerve. The morphology of substance P-like immunoreactive neurons varied according to the subnuclei in which they were found. Three types of tyrosine hydroxylase-like immunoreactive neurons were identified, mainly in the periphery of the dorsal motor nucleus of the vagus nerve, including the medial fringe, ventrointermediate, and dorsointermediate subnuclei of the 10. Many cells throughout the ventrointermediate subnucleus of the dorsal motor nucleus of the vagus nerve are seen ventrally to intermingle with the tyrosine hydroxylase neurons of the intermediate reticular zone. Computer reconstructions provided a three-dimensional view of the positions of substance P- and tyrosine hydroxylase-like immunoreactive neurons within the subdivisions of the dorsal motor nucleus of the vagus nerve. The uneven distribution of substance P- and tyrosine hydroxylase-like immunoreactive neurons within the subdivisions suggests an involvement of these substances in some, but not all, autonomic functions of the dorsal motor nucleus of the vagus nerve.

Mapping of angiotensin II receptor subtype heterogeneity in rat brain.

Angiotensin II (Ang II) exerts a number of central actions on fluid and electrolyte homeostasis, autonomic activity, and neuroendocrine regulation. In order to evaluate likely sites where these actions are mediated, Ang II receptor binding was localized in rat brain by in vitro autoradiography with the aid of the antagonist analogue 125I-[Sar1, Ile8]Ang II. Two subtypes of Ang II receptor have been identified using recently developed peptide and nonpeptide antagonists. In the periphery, the receptor subtypes differ in distribution, second messenger coupling, and function. Brain Ang II receptor subtypes were therefore differentiated into AT-1 (type I) and AT-2 (type II) subtypes by using unlabelled nonpeptide antagonists specific for the two Ang II subtypes. AT-1 binding was determined to be that inhibited by Dup 753 (10 microM) and AT-2 binding to be that inhibited by PD 123177 (10 microM). The reducing agent dithiothreitol (DTT) decreased binding to AT-1 receptors and enhanced binding to AT-2 receptors. Many brain structures, such as the vascular organ of the lamina terminalis, subfornical organ, median preoptic nucleus, area postrema, nucleus of the solitary tract, and dorsal motor nucleus of the vagus, which are known to be related to the central actions of Ang II, contain exclusively AT-1 Ang II receptors. By contrast, the locus coeruleus, ventral and dorsal parts of lateral septum, superior colliculus and subthalamic nucleus, many nuclei of the thalamus, and nuclei of the inferior olive contain predominantly AT-2 Ang II receptors. The detailed binding characteristics of each subtype were determined by competition studies with a series of analogues of angiotensin and antagonists. The pharmacological specificity obtained in rat superior colliculus and the nucleus of the solitary tract agreed well with published data on AT-1 and AT-2 receptors, respectively. There was a high degree of correlation between the distribution of Ang II binding sites with published data on Ang II-immunoreactive fields and on the sites of Ang II-responsive neurons. The present study also reveals pharmacological heterogeneity of brain Ang II receptors. The subtype-specific receptor mapping described here is relevant to understanding the role of angiotensin peptides in the central nervous system and newly discovered central actions of nonpeptide Ang II receptor antagonists.

Organization of the human paraventricular hypothalamic nucleus.

The cyto- and chemoarchitecture of the human paraventricular hypothalamic nucleus (Pa) was studied with the aid of three-dimensional computer reconstruction. The adult human Pa is a vertically elongated structure that abuts the wall of the third ventricle (3V) medially and is indented dorsolaterally by the descending fornix. Chemoarchitecture revealed the following five subnuclei in the human Pa. The most prominent of these is the magnocellular subnucleus (PaM) occupying the ventrolateral quadrant of the Pa and comprised of a concentration of large arginin-vasopressin (AVP)- and acetylcholinesterase (AChE)-positive cells, and small calbindin (Cb)-positive neurons. Rostrally, the PaM is succeeded by the small anterior parvicellular subnucleus (PaAP), which contains small AChE-, AVP- and tyrosin hydroxylase (TH)-positive cells. Dorsal to the PaM is found the dorsal subnucleus (PaD), containing large spindle-shaped TH-, oxytocin (OXY)-, and AChE-positive cells, as well as a population of small Cb-positive neurons. Abutting the wall of the 3V and medial to PaM and PaD is the parvicellular subnucleus (PaP). The PaP contains small cells immunoreactive for corticotropin-releasing factor (CRF), neuromedin K receptor (NK3), and nonphosphorylated neurofilament protein (SMI32). The posterior subnucleus (PaPo) is situated posterior to the descending column of the fornix; it replaces all above-mentioned subdivisions caudally, and is a chemoarchitectonic amalgam that includes dispersed large AChE-, OXY-, AVP- and TH-positive cells, as well as small NK3-, CRF-, SMI32- and Cb-immunoreactive neurons. The present findings suggest that the human PaM and PaD are homologues to the magnocellular subnuclei of the rat Pa, whereas the human PaP and PaPo correspond to the rat medial parvicellular and posterior subnuclei, respectively.

Localization and characterization of angiotensin II receptor binding sites in the human basal ganglia, thalamus, midbrain pons, and cerebellum.

Angiotensin II (Ang II) binding sites were localized in the thalamus, basal ganglia, midbrain, and pons of the human central nervous system by in vitro autoradiography, employing 125I-[Sar1, Ile8]angiotensin II as the radioligand. High-density binding occurs in the substantia nigra pars compacta, the interpeduncular nucleus and two of the raphe nuclei, the raphe magnus, and median raphe nucleus. Moderate densities occur in the caudate nucleus, putamen, bed nucleus of the stria terminalis, rostral linear nucleus, caudal linear nucleus, dorsal and paramedian raphe nuclei, locus coeruleus, and region of the subcoeruleus, oral dorsal paramedian nucleus, and A5/periolivary region. Low levels occur in the region between the subthalamic nucleus and the zona incerta, the mediodorsal thalamic nucleus, the central gray, the lateral and medial parabrachial nuclei, and the molecular layer of the cerebellum. The high density of Ang II receptor binding in the substantia nigra occurs over pigmented, presumably dopaminergic, neurons. The binding in this site, and in the striatum, is not observed in any of the other species we have studied. It displays similar pharmacological characteristics to the Ang II receptor binding site in other regions of the human brain. Overall we demonstrate a discrete pattern of Ang II receptor binding sites in the human brain, which shows a high correlation with the distribution observed in other mammalian species.

Localization and characterization of angiotensin II receptor binding and angiotensin converting enzyme in the human medulla oblongata.

Angiotensin II receptor and angiotensin converting enzyme distributions in the human medulla oblongata were localised by quantitative in vitro autoradiography. Angiotensin II receptors were labelled with the antagonist analogue 125I-[Sar1, Ile8] AII while angiotensin converting enzyme was labelled with 125I-351A, a derivative of the specific converting enzyme inhibitor, lisinopril. Angiotensin II receptor binding and angiotensin converting enzyme are present in high concentrations in the nucleus of the solitary tract, the dorsal motor nucleus of vagus, the rostral and caudal ventrolateral reticular nucleus, and in a band connecting the dorsal and ventral regions. In the rostral and caudal ventrolateral reticular nucleus, angiotensin II receptors are distributed in a punctate pattern that registers with neuronal cell bodies. The distribution and density of these cell bodies closely resemble those of catecholamine-containing neurones mapped by others. In view of the known interactions of angiotensin II with both central and peripheral catecholamine-containing neurons of laboratory animals, the current anatomical findings suggest similar interactions between these neuroactive compounds in the human central nervous system. The presence of angiotensin II receptors and angiotensin converting enzyme in the nucleus of the solitary tract, dorsal motor nucleus of vagus, and rostral and caudal ventrolateral reticular nucleus demonstrates sites for central angiotensin II to exert its known actions on vasopressin release and autonomic functions including blood pressure control. These data also suggest a possible interaction between angiotensin II and central catecholeminergic systems.

Distribution of catecholamine uptake sites in human brain as determined by quantitative [3H] mazindol autoradiography.

Because of the importance of the catecholamine system in Parkinson's disease and its relevance to a variety of clinical movement disorders, catecholamine uptake sites were mapped in the human brain using [3H] mazindol autoradiography. Displacement studies with known dopamine (DA) and noradrenaline (NA) uptake blockers showed that binding in the striatum was to dopamine uptake sites; binding in the locus coeruleus was to noradrenergic uptake sites. By using the selective noradrenergic uptake blocker desmethylimipramine (DMI), a comprehensive map of both DA and NA uptake sites was generated. In general, catecholamine uptake sites were better seen in terminals than in cells of origin or axonal projections. In some areas, such as the locus coeruleus, punctate binding could be seen over individual pigmented cells. A variegated pattern of binding was seen in caudate nucleus and putamen and some correspondence of patches of low binding with striosomes was observed in the caudate. The highest levels of binding to DA uptake sites was observed in the striatum, where regional differences in binding occurred. The most dense binding was seen in the ventral striatum, and a rostral-to-caudal decrement in binding levels in caudate nucleus and putamen was evident. Binding was more intense in the putamen compared to the caudate and within the caudate lower values were seen laterally. The highest levels of binding to noradrenergic uptake sites were in the locus coeruleus and dorsal raphé, although these sites may be on terminals from other projections. Whereas uptake sites were more often evident in known catecholamine pathways, [3H] mazindol binding was seen in some areas where catecholamine neurons or terminals had not been identified previously. These maps of the catecholamine uptake system add further information concerning the nature of the distribution of catecholamines in human brain and provide an important baseline for the study of disease and ageing processes.