Search

Recent studies have shown that at least some of the functional effects of serotonin (5-HT) on motoneuron excitability are direct and are mediated via postsynaptic 5-HT receptors on motoneurons. To determine the spatial distribution of direct inputs from the serotonin system on the proximal and distal dendrites of individual motoneurons, we examined identified motoneurons in vivo with a combination of immunohistochemical localization of 5-HT-immunoreactive boutons and intracellular staining with horseradish peroxidase. Seventeen intracellularly stained motoneurons from 12 adult cats were analyzed with light microscopy. Quantitative analysis of 5-HT boutons apposed to dendrites of five representative motoneurons that were entirely reconstructed in three dimensions (each from the lumbosacral spinal cord of a different animal) revealed a total of 7,848 contacts (1,570+/-487 contacts/postsynaptic neuron; mean +/- SD) over the dendrites of these cells. Analysis of contacts on the soma of two of these cells, and on the somas of an additional 12 intracellularly stained motoneurons, revealed a wide range of somatic contacts (11-211 contacts/cell) on motoneuron cell bodies, with an average of 52 contacts/cell. These results indicate that the vast majority of 5-HT-immunoreactive boutons are apposed to dendritic branches rather than to the somatic surface of motoneurons. The spatial distribution of contacts essentially matched the distribution of surface membrane area of the postsynaptic neuron, resulting in a relatively uniform density of contacts (<1/100 microm2) on proximal and distal dendrites. Consequently, the frequency of contacts was higher on the proximal dendritic compartments where available membrane area is greater. There was no preferential distribution of contacts to particular dendrites. Light/electron microscopic correlations were performed on 21 boutons that contacted dendrites (n = 7) of three motoneurons from different animals. At the electron microscope level, most appositions (18/21; 85.7%) selected by our light microscopic criteria were confirmed as direct contacts when the 5-HT boutons were examined through serial sections. Synaptic junctions, generally small and symmetric, were positively identified in only a subset of these cases (n = 6; 28.6%), in part due to the obscuring effects of the peroxidase histochemical precipitate present in both pre- and postsynaptic profiles. A few 5-HT boutons (3/21; 14.3%) selected as contacts by our light microscopic criteria were in fact separated from the adjacent labeled dendrites; in two of these three cases, the separation was due to intrusion of very thin glial lamellae (<0.3 microm in cross section). These results indicate that the bulbospinal serotonergic system(s) provide a significant, direct synaptic input to spinal motoneurons that innervate hindlimb muscles. The nature of the modulatory actions exerted by such widespread synaptic inputs will affect all regions of the somatodendritic membrane and will ultimately depend on the nature of the 5-HT receptors present over different parts of the postsynaptic neuron's dendritic tree.

The neuronal architecture of the ventrobasal complex (VB) in dog is examined in coronal and horizontal brain sections processed by Golgi- and Nissl-staining methods. Presumed projection and intrinsic neurons are identified by differences in soma size and shape, dendritic branch pattern, the morphology and distribution of appendages, and the appearance of axons. Forty-five projection neurons are examined by quantifying (1) soma cross-sectional area, (2) dendritic field extent and shape, (3) appendages on the soma, primary dendrites, and in a defined major dendritic branch zone, and (4) location in the VB. When considered independently, each variable offers little evidence for separation into morphological classes. However, several of the variables have wide ranges and show significant correlation with other parameters. Using the multivariate descriptive methods of principal components analysis and cluster analysis, a separation of the projection neurons into three morphological classes designated as large, medium, and small neurons is indicated. The features most critical in distinguishing between the groups are, in descending order of importance: (1) dendritic field extent; (2) number of primary dendrites; (3) soma cross-sectional area; (4) number of appendages per major branch point (MBP); (5) number of appendages on the soma; and, (6) number of appendages on the primary dendrites. Dendritic field shape and neuron location have little influence in determining classification.

The histories of exposure to sun through occupational, recreational and vacation activities of 595 patients with newly incident cutaneous melanoma excluding lentigo maligna and acral lentiginous melanoma, were compared to those of comparison subjects drawn randomly from the same population and matched for age, sex and province of residence in Western Canada. Significant increases in risk were seen with increasing amount of sun exposure through outdoor activities associated with recreation and vacations; activities likely to involve more intense sun exposure were associated with greater increases in risk. While a moderate amount of occupational exposure was associated with increased risk, greater occupational exposure resulted in no further increase; in men a decrease in risk was seen. These findings were independent of the effects of hair and skin colour, freckles, ethnic origin and socio-economic status. The results suggest that short-term exposure to unusually intense sunlight increases the risk of melanoma, while long-term constant exposure has no effect or may decrease risk. No simple relationship was seen between melanoma risk and total sunlight exposure. This study introduces new methods of assessing different types of sun exposure from retrospective data.

The topographic arrangement and cytoarchitecture of cells in the ventral posterolateral nucleus (VPL) of a prosimian primate (Galago senegalensis) were studied using horseradish peroxidase (HRP) and Golgi impregnation techniques. Following cortical implants of HRP, reactive neurons in VPL are organized into medially concave lamellae which extend through the dorsoventral and rostrocaudal dimensions of the nucleus. After implant in forelimb and hindlimb areas of motor-sensory cortex, labeled cells are confined to the medial (VPLm) and lateral (VPLl) portions of VPL, respectively. HRP-positive cells in the ventral part of each lamella are organized into clusters which correspond to the clusters of cells and "parcellated-bursts" of preterminal debris previously described in bushbaby VPL (Pearson and Haines, this volume). HRP-reactive cells in the ventral intermediate nucleus (Vim) are evenly distributed as contrasted to the tightly clustered groups of somata in the adjacent VPL. This evidence argues in favor of the presence of Vim in dorsal thalamus of this prosimian. Golgi impregnations reveal two main types of relay cells in Galago VPL. Type I cells have multiangular somata, straight distal dendrites, and primary dendritic branch points which are free of appendages. Tye II cells have rounded somata, sinuous distal dendrites, and clusters of appendages located at primary branch points. Intermediate cells (i.e., cells with morphological features in between types I and II) are also present in VPL. Comparison of tufted Golgi impregnated cells with neurons labeled with HRP shows definite similarities in somata size and shape, and in the orientation of proximal dendrites. This evidence corroborates the relay nature of the tufted neurons in VPL. Relay cells in Galago VPL have morphological features which are similar to those of relay cells in lateral and medial geniculate nuclei of cat and primate. Type III cells have small round somata, radiate dendrites with elaborate appendages, and axons which appear to be intrinsic to VPL. Consequently, these cells are considered to be interneurons in the VPL of Galago. Glial-like neurons (type IV cells) were also observed. These have beaded dendritic processes similar to those which presumably represent presynaptic boutons in other species. Consequently, these cells are also assumed to function intrinsically within VPL.

The configuration of somatosensory relay nuclei and termination of spinothalamic fibers were studied in the dorsal thalamus of a prosimian primate(Galago senegalensis) using Nissl, Klüver and Barrera ('53), Weil ('45), and Fink and Heimer ('67) methods. The ventral posterolateral nucleus (VPL) is divided into medial and lateral parts (VPLm and VPLl, respectively) by a sheet-like lamina of fibers. Spinothalamic input to Galago VPL is somatopically arranged; input from the forelimb terminates in VPLm and that from hindlimb in VPLl. In addition, preterminal debris in caudal VPL is dense and organized into "parcellated bursts" (terminology of Mehler, '69). Consequently, the nature of the spinothalamic debris in VPL of Galago is similar to that reported for higher primates (Mehler et al., '60). Located dorsomedial to the rostral extension of VPL is a zone of large, deeply staining cells designated as the ventral intermediate nucleus (Vim). Following hemisection at either cervical or lumbar spinal cord levels, preterminal debris, independent of that coursing into VPL, enters the Vim. This substantiates the presence of an intermediate nucleus (i.e., Vim) between VPL and the more rostral ventral lateral nucleus. In the medial thalamic region, axonal degeneration is located in the central lateral nucleus (CL) and in the densocellular and the multiform portions of the dorsomedial nucleus. Only fibers of passage are identified in the centre median, the paracentral and the subparacentral nuclei. The posterior nuclear group (PO) in Galago is divided into medial and lateral parts designated as POm and POl, respectively. In addition, PO contains three distinct nuclei: 1) the magnocellular (MC) portion of the medial geniculate nucleus; 2) the nucleus limitans (Lim); and 3) the suprageniculate nucleus (SG). Following spinal cord hemisection, preterminal debris is located throughout the POm and around cells of the MC. Lim and SG contain no discernible degeneration. Preterminals are also found in a group of cells designated as the caudal part of the central lateral nucleus (CLC).

The morphology of neurons in the subthalamic nucleus (STN) of the lesser bushbaby (Galago senegalensis) is described in coronal brain sections processed by Golgi- and Nissl-staining techniques. Quantitative and statistical methods are used to evaluate (1) soma size and shape, (2) dendritic field size, shape, and branch frequency, (3) the number of dendritic and somatic spines per neuron, and (4) neuron location within the STN. Principal components analysis of these variables suggests that three classes of neurons are present. Two of these classes are considered to be projection cells, referred to as elongate-fusiform and radiate neurons, respectively. Elongatefusiform neurons have somata and dendritic fields which are large in diameter, extremely fusiform in shape, and give rise to few appendages. Somata and dendritic fields of radiate neurons are smaller in diameter, more rounded in shape, and support more spines than the elongate-fusiform neurons. The third class of cells in Galago STN is tentatively identified as consisting of interneurons on the basis of small soma and dendritic field size, thin and varicose dendritic morphology, and the presence of multilobulated dendritic appendages.

The morphology of neurons in the centromedian (CM) and parafascicular (PF) nuclei in the lesser bushbaby (Galago senegalensis) is described in coronal and horizontal brain sections using Golgi-, horseradish peroxidase (HRP)-, and Nissl-staining procedures. The CM contains two types of cells referred to as principal neurons and Golgi type II (like) neurons. Cell bodies of principal neurons are relatively large in cross-sectional area (mean = 130.42 micron2), round to spindle in shape, support short somatic spines, and give rise to three to five primary dendrites. The dendrites branch in a "radiate" pattern and possess numerous appendages consisting of narrow, stalk-supported swellings. The presumed axons of these cells are impregnated only in their initial segments. On the basis of the similarity of principal neuron soma shapes and cross-sectional areas with those of HRP-reactive somata following cortical HRP implantation, it is concluded that at least some of the principal neurons in Galago CM project to somatic sensory-motor cortex. Golgi type II (like) neurons have small (mean = 79.43 micron2), round somata which support several spines and give rise to three to four small-diameter dendrites. The dendrites are infrequently branched, sinuous in their courses, and give rise to complex appendages and beaded processes. However, the axons of these cells could not be seen to ramify in the immediate vicinity of the dendritic field or soma, and there is considerable overlap in the cross-sectional areas of Golgi type II (like) neurons seen in Golgi preparations and HRP-stained cells following cortical implant of HRP pellets. Consequently, although Golgi type II (like) cells have traits characteristic of classically described intrinsic neurons, a cortical projection of these cells cannot be ruled out by the present study. The parafascicular nucleus contains two groups of large, radiate cells characterized by the presence or absence of somatic spines. Cells with somatic spines also contain numerous appendages on the dendrites. Cells without somatic spines support only a few, isolated, short dendritic appendages. Numerous small cell-bodied neurons are present in Nissl-stained sections of PF; however, cells which resemble Golgi type II neurons were not observed in the PF in the present Golgi-impregnated material. In contrast to the CM, the large cell-bodied neurons in PF were not found to project to somatic sensory-motor cortex in Galago.

A case-control study of 374 patients with primary epithelial cancers of the oral cavity, oro- and hypopharynx, and larynx is reported, the controls being patients with selected other cancers, matched for age and sex. Of all eligible patients, 93% were interviewed. Increased risks were seen with alcohol consumption and, less strongly, with smoking, which for all sites could be adequately fitted by either a multiplicative or an additive model. However, the site-specific relationships were different, alcohol consumption being significantly associated only with oral cavity, pharyngeal and extrinsic laryngeal tumours, and smoking only with intrinsic laryngeal tumours. Increased risks were associated with low socio-economic status, the unmarried state, and poor dental care. No significant associations were seen with specific occupational exposures.