Distribution of substance P-like immunoreactive neurons and terminals throughout the nucleus of the solitary tract in the human brainstem.

The anatomical distribution of substance P-like immunoreactivity across the subnuclear divisions of the nucleus of the solitary tract has been examined in the human medulla oblongata. A differential distribution of neurons, fibres, and terminals was observed throughout the ten subnuclear divisions of this nucleus. Substance P-like immunoreactive neurons were observed most frequently in the nucleus gelatinosus, with moderate numbers in the medial, intermediate subnuclei and very few in the commissural, ventral, dorsal, and dorsolateral subnuclei. The paracommissural, ventrolateral, and interstitial subnuclei did not contain substance P-like-immunoreactive neurons. These neurons were typically bipolar and moderate-sized to large, except for the neurons in the nucleus gelatinosus, which were substantially smaller. The highest densities of fibres and terminals were observed in the gelatinosus, medial, and intermediate nuclei, with moderate densities in the paracommissural and dorsal subnuclei. Sparse substance P-like-immunoreactive fibres and terminals were seen in the ventral and interstitial nuclei as well as within the solitary tract. The dorsolateral nucleus was characterized by a light distribution of fibres and terminals, except for a dense aggregation along its lateralmost border. A prominent innervation of pigmented neurons by substance P-like-immunoreactive terminals and fibres was also observed in the dorsolateral nucleus. The results reveal that the subnuclear complexity of the nucleus of the solitary tract is richly reflected by its differential pattern of substance P-like-immunoreactive structures.

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.

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.

Serotoninergic innervation of area 17 in the cat.

Three morphological types of axons have been recognized in previous studies of the serotoninergic (5-HT) innervation of the cat cerebral cortex (Mulligan and Törk, 1988; DeFelipe et al., 1991): thick, nonvaricose axons, fine axons with small varicosities, and beaded axons with large, spherical varicosities. In the present study, the laminar density and distribution of the three 5-HT fiber types in area 17 are characterized. In both coronal and sagittal immunostained sections, 5-HT axons exhibit an overall gradient of decreasing density from layer I to the white matter. The three 5-HT axon types exhibit distinctive innervation patterns. (1) Fine axons with small varicosities comprise the greatest number of fibers in each layer (56-98%). They usually have oblique or radial trajectories, but some horizontally oriented fibers run through layers I, III, VI, and the white matter. (2) Non-varicose axons, the preterminal portions of the beaded axons with the large varicosities (Mulligan and Törk, 1988), comprise only about 7% of the total 5-HT fiber population in area 17, and are found mainly in layer I and in the white matter where they form a horizontally oriented plexus. (3) Large varicose axons ("beaded" axons) are rare (about 3% of the total 5-HT population) and are restricted to layers I and V. Although large varicose axons often form elaborate pericellular basketlike arbors around the soma and dendrites of neurons in other parts of the cat cerebral cortex (Mulligan and Törk, 1987, 1988), such arrays are rare in area 17. When observed in area 17, pericellular arrays are typically simple structures with a few large varicosities apparently contacting only the somata of a small population of layer I neurons. Comparison of these results with reports of 5-HT innervation of area 17 in other species suggests that the 5-HT innervation of the cortex is highly species specific.

The internal organization of the human solitary nucleus.

The present study examines the topography and cytoarchitecture of the solitary nucleus (Sol). Three human medulla oblongatae were serially sectioned and alternate sections were reacted for the enzyme acetylcholinesterase or stained with cresyl violet. The 10 component subnuclei of Sol were identified on the basis of their acetylcholinesterase reactivity and cytoarchitecture. These subnuclei are the paracommissural, commissural, gelatinosus, medial, ventral, ventrolateral, dorsal, dorsolateral, intermediate, and interstitial. Cytoarchitecturally, Sol is characterised by an abundance of small cells of varied morphology but also features some medium to large cells as well as pigmented neurons which are differentially distributed across the subnuclei. From spaced serial sections, the outlines of the subnuclei and the entire Sol were used to create three-dimensional computer reconstructions to display the position and extent of each component subnucleus. Our results show that the internal architecture of the human solitary nucleus is similar to that of rodents and carnivores, though there are some notable species differences.

Morphology and distribution of neuropeptide-containing neurons in human cerebral cortex.

Biopsies of human cerebral cortex were fixed by immersion and immunostained for the detection of neuropeptides in neuronal cell bodies and axons. Four neuropeptides (neuropeptide Y, somatostatin, , substance P and cholecystokinin) were visualized in a series of adjacent sections. All populations of immunoreactive neurons had a morphology characteristic of interneurons, with variations in dendritic arborizations and laminar distribution. The cholecystokinin-immunoreactive neurons were most numerous in the supragranular layers, whereas neurons containing the other three peptides occurred mainly in infragranular layers, or even in neurons populating the subcortical white matter. Quantitatively, each population of neuropeptide-containing neurons accounted for 1.4-2.5% of the total neuronal population. The distribution of these neurons varied slightly between cytoarchitectonic divisions, with substance P- and somatostatin-immunoreactive neurons dominating in the temporal lobe and cholecystokinin-immunoreactive neurons in the frontal lobe. Neuropeptide Y-immunoreactive neurons dominated in the gray matter of the frontal half of the hemisphere and in the subcortical white matter of the caudal half of the hemisphere. Furthermore, co-existence of neuropeptide Y or substance P immunoreactivity within somatostatin-immunoreactive neurons could be demonstrated using double labeling immunofluorescence techniques. The axonal plexuses immunoreactive for neuropeptide Y, somatostatin, or substance P were distributed in all layers, with a strong predominance of horizontally oriented fibers in layer I, a moderate plexus of randomly oriented fibers in the supra- and infragranular layers, and a slightly weaker innervation of layer IV. Immunoreactive axons formed, in addition, complex terminal arbors, mostly in older subjects, suggesting that they resulted from an as yet undefined aging process. The present study underlines several aspects of the organization of the neuropeptide-containing neurons of the human cerebral cortex, which are of particular interest in the light of the involvement of these neurons in several neurodegenerative diseases.

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.

Differential development of the dual serotoninergic fiber system in the cerebral cortex of the cat.

The changes in distribution and density of the serotoninergic innervation of the cerebral cortex were studied in kittens from birth (PO) to 60 days of age (P59). Three cortical areas were sampled: prefrontal, primary auditory, and primary visual areas. Two systems of serotoninergic axons were demonstrated by immunocytochemical techniques: the fine axon system characterized by small fusiform varicosities up to 1 micron in diameter, and the beaded axon system, the fibers of which have round varicosities up to 5 microns in diameter. The density of the two types of fibers across the cortical layers at different ages was measured with a semiautomatic computerized system. In all three areas, the density of fine axons increased steadily from birth, although the pattern of innervation changed from an even distribution at PO to a distinct concentration of the fibers in layers I-III by week 2 in the prefrontal cortex and by week 3 in auditory and visual cortices. By contrast, the beaded axons first appeared in the cortex at week 2 for the prefrontal cortex, at week 3 in auditory and visual areas. Initially, these fibers were distributed throughout all cortical layers and were of much lower density than the fine axons. At later ages the beaded axons became confined to layers I-III where they gradually increased in number, and from week 4, they formed pericellular arrays which were only observed in the prefrontal and auditory cortices, not in visual cortex. These findings provide further evidence for the existence of two parallel subsystems of serotoninergic axons which are different not only in their morphology and nuclear origin, but also in their development. Our finding that the two serotoninergic fiber systems arrive in the cortex in two different stages suggests that they have differential roles in development. The late formation of the pericellular arrays indicates that the formation of the specific connections made by the beaded fibers could be dependent on a certain degree of maturity of the target neurons.

Cytoarchitecture of serotonin-synthesizing neurons in the pontine tegmentum of the human brain.

We have employed immunohistochemical and morphometric procedures to study serotonin-synthesizing (PH8-immunoreactive) neurons in the pontine reticular formation of the adult human. PH8-immunoreactive neurons were found in three cytoarchitectural regions: the median raphe nucleus (MnR), oral pontine reticular nucleus (PnO), and supralemniscal region (group B9). On the basis of cell size, morphology, and position, it was possible to distinguish distinct subgroups within the MnR (dorsal, midline, and paramedian cell clusters) and within the PnO (dorsal and central cell clusters), whereas within the B9 there were no distinct cell clusters. We have estimated that there are approximately 125,000 PH8-immunoreactive neurons in the human pontine tegmentum; 64,400 in the MnR, 30,700 in PnO and 29,000 in B9. The large numbers of serotonin-synthesizing neurons in the human pontine tegmentum contrasts with their relative paucity in nonprimate species such as rats and cats. Nonhuman primates also have large numbers of pontine serotonergic neurons but the morphology of these neurons and their spatial arrangement is significantly different in humans. These results are discussed with respect to the possible projections and functions of these neurons in humans.

Distribution, morphology and number of monoamine-synthesizing and substance P-containing neurons in the human dorsal raphe nucleus.

The distribution, morphology and number of serotonin-, catecholamine- and substance P-containing neurons in the human dorsal raphe nucleus were studied. Parallel series of sections were prepared from 10 human brainstems obtained at autopsy from patients without neurological disease aged between 42 and 88 years. The neurons were identified using immunohistochemistry with antibodies raised against phenylalanine hydroxylase (tryptophan hydroxylase-containing, serotonin neurons), tyrosine hydroxylase (catecholamine neurons) and substance P. A reference series of Nissl-stained sections was also prepared and data published separately were used to delineate the subnuclear divisions of the dorsal raphe nucleus and to establish the total number of neurons in each subnucleus. The following principal findings emerged. (1) Serotonin-synthesizing neurons are present in all regions of the dorsal raphe nucleus and their total number is 165,000 +/- 34,000. The same types of neurons as those seen in Nissl material characterize each of the five subnuclei (caudal, dorsal, ventral, ventrolateral and interfascicular). (2) Substance P-containing neurons mostly occupy the rostral part of the nucleus and their number is 74,600 +/- 17,600. (3) Catecholamine cells are only found in the rostral part of the dorsal raphe nucleus and their number is 5600 +/- 3400. (4) In the ventral and interfascicular subnuclei the combined number of serotonin-synthesizing and substance P-containing neurons exceeds the total number of Nissl-stained neurons suggesting that serotonin and substance P co-exist in a substantial part of the cell population of the dorsal raphe nucleus. This is further supported by the highly similar morphology and size of these neurons. It is concluded that there are demonstrable chemical differences between the various subregions of the human dorsal raphe nucleus. These differences are in harmony with the results of hodological studies in animals, which have demonstrated differential projection pathways emerging from this nucleus.

Cytoarchitecture of the human dorsal raphe nucleus.

Serial 50 microns Nissl-stained sections through the midbrain and pontine central gray of four adult humans (mean age 56 years, mean postmortem delay 3 hours) were analysed and the subnuclei of the dorsal raphe nucleus (DR) delineated on the basis of neuronal morphology and density. Five subnuclei were apparent: the interfascicular, ventral, ventrolateral, dorsal, and caudal. The area of each subnucleus was measured in sections selected at regular intervals throughout the length of the DR. The number of neurons was counted and their density within each subnucleus calculated. The dorsal subnucleus was the largest and contained the majority of neurons but had the lowest neuronal density. The ventrolateral subnucleus had the highest density of neurons. A total of 235,000 +/- 15,000 neurons (average of 1,200 +/- 200 neurons per section) were found within a volume of 71.3 +/- 4.5 mm3 of DR with a mean neuronal density of 3,300 +/- 200 neurons/mm3. Morphometric and morphological analysis of DR neurons revealed four distinct neuron types: round, ovoid, fusiform, and triangular. These types of neurons characterized particular subnuclei. The location and boundaries of the subnuclei of the human dorsal raphe are presented in the form of an atlas. The subdivisions described are similar to that described in other mammals. On the basis of this information the location of particular projection neurons within the human dorsal raphe can be predicted and the effects of disease on this nucleus may be forecast.

Distribution of two morphologically distinct subsets of serotoninergic axons in the cerebral cortex of the marmoset.

The serotoninergic innervation of the marmoset (New World monkey, Callithrix jacchus) cerebral cortex has been analyzed by using immunocytochemistry. The use of a sensitive monoclonal antibody against serotonin allowed the visualization of the fine morphology of individual axons. Two types of terminal axons were demonstrated: one has sparse, small, ovoid varicosities (dia. less than 1 micron), and the other has large, spheroidal varicosities (up to 5 microns in dia.), which are more densely clustered. The first type of axon is distributed through all cortical layers, with a characteristic laminar distribution that varies from area to area. The second type of axons was distributed sparsely in all regions but was markedly denser in the frontal and anterior parietal lobes, and in the hippocampal formation. Axons with large varicosities typically surrounded certain cell bodies and proximal dendrites, forming pericellular arrays, or baskets. These morphological specializations were most frequent in the frontal and anterior parietal cortex, where they were found around stellate and horizontal cells in layer I and around stellate and bipolar cells in layer II and III. Similar baskets were also found in the hippocampal formation, mainly along the border between the hilus and the granule cell layer of the dentate gyrus, across the CA4 field, and at each side of the pyramidal cell layer of the CA3 regions. The distribution and cellular morphology of the cell surrounded by the 5-HT basket fibres were suggestive of a subpopulation of interneurons, possibly GABAergic and/or peptidergic. In agreement with previous reports on the innervation of the cerebral cortex of other mammalian species, the marmoset cerebral cortex is innervated by two separate subsystems of serotoninergic axons. One of these may have a strong and specific influence on the cortical inhibitory circuitry, via relay through cortical interneurons.

Distribution of substance P-like immunoreactive fibres and terminals in the medulla oblongata of the human infant.

This study provides a detailed report of the distribution and density of substance P-like immunoreactive fibres and terminals within the human infant medulla. Seven brains with no signs of macroscopic alteration fixed usually within 24-48 h after death were used. Free floating transverse sections (50-60 microns) were then immunostained with a monoclonal antibody against substance P using the avidin-biotin-peroxidase technique. Morphologically three types of substance P-like immunoreactive fibres were observed: those with small varicosities of less than 1 micron, those with medium varicosities of 1-2 microns and those with large varicosities of 2-4 microns. Very dense substance P-like immunoreactivity was present within the spinal trigeminal nucleus, parts of the gracile and cuneate fasciculi and the paracommissural subnucleus of the solitary nucleus; dense substance P-like immunoreactivity was present within the dorsal nucleus of the vagus nerve, commissural, medial, dorsal, dorsolateral ventral and ventrolateral subnuclei of the solitary nuclear complex, parasolitary nucleus, raphe obscurus, inferior olivary complex (medial, dorsal, dorsomedial nuclei) and ventrolateral part of the dorsal reticular nucleus; moderate substance P-like immunoreactivity was present within the gelatinosus nucleus of the solitary tract, lateral reticular nucleus proper, intermediate reticular zone and parvocellular reticular nucleus; sparse substance P-like immunoreactivity was present within the hypoglossal nucleus, retroambigual nucleus and much of the reticular formation (dorsal, parvocellular, ventral gigantocellular, dorsal paragigantocellular nuclei): and very sparse substance P-like immunoreactivity was present within the nucleus ambiguus, medial vestibular nucleus and parts of the reticular formation (ventral, medial, gigantocellular, ventral gigantocellular, dorsal paragigantocellular nuclei). Substance P-like immunoreactivity was absent in the area postrema, intercalated nucleus, gracile and cuneate nuclei, in the epiolivary, subtrigeminal and parvocellular divisions of the lateral reticular nucleus, spinal vestibular nucleus, and in the solitary and pyramidal tracts. In several regions the substance P-like immunoreactive fibres formed distinct pericellular arrays around the somata and dendrites of neurons (hypoglossal nucleus, dorsal nucleus of the vagus nerve, retroambigual nucleus, intermediate reticular zone). The results indicate the high specificity of the localization of substance P in various structures of the brainstem and underline the presumed significance of this peptide in autonomic and sensorimotor functions of the brain.

Serotonin-like immunoreactive cells and fibres in the rat ventromedial mesencephalic tegmentum.

The distribution and morphology of serotonin-like immunoreactive (5HT-IR) nerve cells, fibres and terminals in the rat ventromedial mesencephalic tegmentum (VMT) was studied using qualitative and quantitative immunohistochemical methods at light and electron microscopic levels. All five component nuclei were examined and the size, number and density of immunoreactive neurons and terminals determined. Thirty percent of all neurons in the caudal linear nucleus and 1% in the interfascicular nucleus were immunoreactive for serotonin. Different regions of the VMT had morphologically distinct 5HT-IR fibres and quantitative differences between the VMT nuclei were seen in the density of 5HT-IR terminals. In the lateral VMT, many thick, nonvaricose 5HT-IR fibres were found in the parabrachial pigmented nucleus while many fine, varicose 5HT-IR fibres were found in the paranigral nucleus. Fine, varicose 5HT-IR fibres were also seen in the rostral and caudal linear nuclei. Many 5HT-IR axon profiles formed synapses with small calibre dendrites. 5HT-IR fibres in the interfascicular nucleus were thick with variable sized varicosities at irregular intervals. Few 5HT-IR axon profiles formed synapses in this nucleus. A comparison between the number of 5HT-IR terminals and the total number of axon terminals in the VMT (25) reveals that the majority of all terminals in the paranigral and rostral linear nuclei can be labelled with serotonin. The effect of serotonin on VMT cells is therefore likely to be mediated by different types of 5HT-IR fibres which preferentially innervate particular VMT nuclei.

The human locus coeruleus complex: an immunohistochemical and three dimensional reconstruction study.

The CA (catecholamine/catecholaminergic) cell populations of the locus coeruleus (LC) and subcoeruleus (SubC) were studied using serial sections of the human brainstem immunostained with an antibody against tyrosine hydroxylase. The tyrosine hydroxylase-immunoreactive (TH-IR) neurons were plotted in a computer reconstruction system and their number and soma size determined. Serial section computer analysis was then used to create a three dimensional reconstruction of the LC complex. The number of cells containing neuromelanin pigment was also determined and compared with the number of TH-IR cells. In our sample there were 53,900 TH-IR cells in the LC and a further 6260 cells in the SubC. These numbers were very similar to our estimates of the number of cells containing neuromelanin pigment and we concluded that virtually all of these cells were also tyrosine hydroxylase positive. The average soma size of the TH-IR cells of the LC was 37 microns and in the SubC 34 microns. In addition to these quantitative observations the morphology of the TH-IR and the Nissl stained cells is described in some detail. We also compared the groups of immunoreactive cells in the human pons with the noradrenergic groups A5-A7 described in the rat. Although in the human these groups are contiguous, A5 is not part of the LC complex. However we did find that the A7 group is equivalent to the rostroventral part of SubC while the remainder of SubC is formed by ventral A6.

Morphology of tyrosine hydroxylase-immunoreactive neurons in the human cerebral cortex.

In freshly fixed biopsies of human cerebral cortex obtained at surgery, immunocytochemical staining with antibodies against tyrosine hydroxylase (the rate limiting biosynthetic enzyme for catecholamines) revealed, in addition to a dense axonal plexus, a population of immunoreactive cell bodies. The neuronal nature of these cells was ascertained by: i) the presence of a rich rough endoplasmic reticulum in the cell body and of synapses on the cell body and dendrites, and ii) the demonstration of the lack of reactivity with the astroglial marker, glial fibrillary acidic protein, in the tyrosine hydroxylase-immunoreactive cells. The tyrosine hydroxylase-immunoreactive neurons were found in all areas of cortex sampled, and were located almost exclusively in the infragranular layers. Most tyrosine hydroxylase-immunoreactive cells were bipolar and were vertically oriented, but a few had a multipolar or horizontal dendritic arbor. The dendrites of these cells were varicose and aspiny, and the axons were very thin. Tyrosine hydroxylase-immunoreactive neurons were reported to be present transiently in the developing mammalian cerebral cortex and only recently in cerebral cortex of mature mammalian brains. Internuncial neurons in the human cerebral cortex containing a catecholamine synthesizing enzyme would be significant, in particular considering that catecholamines are likely to be involved in some major mental disorders.

Substance P-like immunoreactive fibres in the ventromedial mesencephalic tegmentum of rat.

The distribution and morphology of the substance P-like immunoreactive (SP-IR) fibres and terminals in the rat ventromedial mesencephalic tegmentum (VMT) were studied using qualitative and quantitative immunohistochemical methods at light and electron microscopic levels. All five component nuclei of the VMT were examined and the size, number and density of immunoreactive terminals determined. The SP-IR fibres were distributed heterogeneously within the VMT. Under the electron microscope, SP-IR axon terminals contained both clear and dense-cored vesicles and made both symmetrical and asymmetrical synapses. The ultrastructure of the SP-IR terminals appeared to differ between nuclei. Small, clear vesicle terminals made symmetrical synaptic junctions with small calibre dendrites in the paranigral nucleus while large, clear and dense-cored vesicle terminals made asymmetrical junctions with somata and large calibre dendrites in the interfascicular nucleus. Quantitative differences between the VMT nuclei were also seen in the density of SP-IR terminals, the paranigral nucleus contained the highest density and the rostral linear nucleus the lowest. A comparison between the number of SP-IR terminals and the total number of axon terminals in the VMT reveals that the majority of all terminals in the paranigral nucleus were SP-IR, as well as the majority of axosomatic synapses in the interfascicular nucleus. These regional differences in the SP-IR innervation suggest that substance P and related peptides may perform several specific functions within the VMT and therefore have a more variable influence on this region than was previously thought.