Search PubMed⌕ Search

Biomedical subjects

Y Smith

Publications and source records attributed to Y Smith.

At least 37 records · Page 2Linked to original sources
PubMed2000

Subcortical projections of area 25 (subgenual cortex) of the macaque monkey.

In several species, including primates, stimulation studies indicate that the infralimbic cortex, the most caudal part of the ventromedial prefrontal cortex, functions as a visceral motor region. In addition, recent positron emission tomography studies implicate the subgenual region in depression and mania. To determine the subcortical projections of this region in primates, injections of Phaseolus vulgaris leukoagglutinin, biotinylated dextran amine, or rhodamine-labeled dextran amine were placed in area 25 in three monkeys. In contrast to the efferents from area 25 previously described in the rat, there were no projections to autonomic effector regions, such as the nucleus of the solitary tract, magnocellular neurosecretory cell groups in the hypothalamus, ventrolateral medulla, or intermediolateral column of the spinal cord. However, projections were shown to a number of structures with probable roles in autonomic function and direct connections to some of the abovementioned autonomic effector regions, including bed nucleus of the stria terminalis, perifornical and anterior hypothalamus, periaqueductal gray, and lateral parabrachial nucleus. In addition, there were projections to several forebrain structures that receive projections from other components of the medial prefrontal network including the medial part of the caudate nucleus, lateral septum, midline and mediodorsal thalamic nuclei, the lateral parvocellular part of the basal accessory amygdaloid nucleus, and the magnocellular part of the basal amygdaloid. None of the injections resulted in labeling in the medulla. These connections support the idea of a role for cortical area 25 in emotional and autonomic responses, albeit less direct than that described in rodents.

Animals↗
PubMed2000

CART peptides.

CART peptides are among the newest putative peptide neurotransmitter/cotransmitters. They show no significant homology to any other peptide, and they are thought to have a role in reward and reinforcement, feeding, development, sensory processing, stress and endocrine control.

Amino Acid Sequence↗
PubMed2000

Differential innervation of parvalbumin-immunoreactive interneurons of the basolateral amygdaloid complex by cortical and intrinsic inputs.

In the basolateral (BL) amygdaloid complex, the excitability of projection cells is regulated by intrinsic inhibitory interneurons using gamma-aminobutyric acid (GABA) as a transmitter. A subset of these cells are labeled in a Golgi-like manner by Parvalbumin (PV) immunohistochemistry. Recently, we have shown that the overwhelming majority of axon terminals contacting these PV-immunoreactive neurons form asymmetric synapses. The present study was undertaken to identify the source(s) of these inputs. Since previous work had revealed that thalamic axons form very few synapses on BL interneurons (< 1%), we focused on cortical and intra-amygdaloid inputs. Iontophoretic injections of the anterograde tracers Phaseolus vulgaris-leucoagglutinin or biotinylated dextran amine were performed in various cortical fields in cats (perirhinal, entorhinal, pre/infralimbic cortices) and monkeys (orbitofrontal region) or in the BL amygdaloid nucleus in cats. These injections resulted in a large number of anterogradely labeled terminals forming asymmetric synapses in the BL complex. Following cortical injections, numerous anterogradely labeled terminals were found in the vicinity of PV-immunoreactive interneurons in the BL amygdala. However, only approximately 1% of these terminals formed synaptic contacts with PV-immunoreactive profiles. In contrast, as many as 11% of the terminals contributed by the intranuclear axon collaterals of BL projection cells established synapses with PV-immunoreactive elements. Since the axon terminals of PV-immunoreactive interneurons are enriched in GABA and they exclusively form symmetric synapses, these results suggest that PV-immunoreactive interneurons are predominantly involved in feedback inhibition in the BL amygdaloid complex.

Amygdala↗
PubMed2000

CART peptide immunoreactivity in the hypothalamus and pituitary in monkeys: analysis of ultrastructural features and synaptic connections in the paraventricular nucleus.

Cocaine and amphetamine regulated transcript (CART) has been identified as one of the most abundant mRNAs in the rat hypothalamus. The objective of the present study was to elucidate the distribution of CART peptide immunoreactive (CARTir) neurons in the monkey hypothalamus and characterize their ultrastructural features and synaptic connections in the paraventricular nucleus (PVN). CARTir neurons were particularly abundant in the PVN, supraoptic nucleus (SON), infundibular nucleus, and premammillary nucleus, whereas the anterior, lateral, and posterior hypothalamic areas as well as the posterior nucleus displayed moderate immunoreactivity. Dense bundles of CARTir fibers exited the PVN and SON and followed a trajectory to the infundibulum similar to that previously shown for vasopressin and oxytocin fibers. The posterior pituitary was densely packed with large CARTir varicosities which, in some cases, were apposed to labeled pituicytes. The external/palisade zone of the median eminence contained rich plexuses of small CARTir varicose fibers, and the internal/fibrous zone was enriched in large axon-like processes. Electron microscope analysis of the PVN revealed (1) that CART peptide immunoreactivity is found in neurosecretory and non-neurosecretory neurons contacted predominantly by unlabelled terminals forming asymmetric synapses, (2) that CARTir terminals resemble glutamatergic and/or noradrenergic boutons and form asymmetric synapses with non-neurosecretory dendrites, and (3) that neuropeptide Y (NPY)-containing terminals are apposed to CARTir neurons in the medial part of the nucleus. In conclusion, our findings demonstrate that CART peptide is abundant in neuronal perikarya and axon terminals throughout the monkey hypothalamus and along the hypothalamopituitary axis. This strengthens the idea that CART peptides may act as putative neurotansmitters/neuromodulators that mediate various neuroendocrine and autonomic functions in primates.

Animals↗
PubMed2000

Pre- and postsynaptic localization of GABA(B) receptors in the basal ganglia in monkeys.

GABAergic neurotransmission involves ionotropic GABA(A) and metabotropic GABA(B) receptor subtypes. Although fast inhibitory transmission through GABA(A) receptors activation is commonly found in the basal ganglia, the functions as well as the cellular and subcellular localization of GABA(B) receptors are still poorly known. Polyclonal antibodies that specifically recognize the GABA(B)R1 receptor subunit were produced and used for immunocytochemical localization of these receptors at the light and electron microscope levels in the monkey basal ganglia. Western blot analysis of monkey brain homogenates revealed that these antibodies reacted specifically with two native proteins corresponding to the size of the two splice variants GABA(B)R1a and GABA(B)R1b. Preadsorption of the purified antiserum with synthetic peptides demonstrated that these antibodies recognize specifically GABA(B)R1 receptors with no cross-reactivity with GABA(B)R2 receptors. Overall, the distribution of GABA(B)R1 immunoreactivity throughout the monkey brain correlates with previous GABA(B) ligand binding studies and in situ hybridization data as well as with recent immunocytochemical studies in rodents. GABA(B)R1-immunoreactive cell bodies were found in all basal ganglia nuclei but the intensity of immunostaining varied among neuronal populations in each nucleus. In the striatum, interneurons were more strongly stained than medium-sized projection neurons while in the substantia nigra, dopaminergic neurons of the pars compacta were much more intensely labeled than GABAergic neurons of the pars reticulata. In the subthalamic nucleus, clear immunonegative neuronal perikarya were intermingled with numerous GABA(B)R1-immunoreactive cells. Moderate GABA(B)R1 immunoreactivity was observed in neuronal perikarya and dendritic processes throughout the external and internal pallidal segments. At the electron microscope level, GABA(B)R1 immunoreactivity was commonly found in neuronal cell bodies and dendrites in every basal ganglia nuclei. Many dendritic spines also displayed GABA(B)R1 immunoreactivity in the striatum. In addition to strong postsynaptic labeling, GABA(B)R1-immunoreactive preterminal axonal segments and axon terminals were frequently encountered throughout the basal ganglia components. The majority of labeled terminals displayed the ultrastructural features of glutamatergic boutons and formed asymmetric synapses. In the striatum, GABA(B)R1-containing boutons resembled terminals of cortical origin, while in the globus pallidus and substantia nigra, subthalamic-like terminals were labeled. Overall, these findings demonstrate that GABA(B) receptors are widely distributed and located to subserve both pre- and postsynaptic roles in controlling synaptic transmission in the primate basal ganglia.

Animals↗
PubMed2000

Anatomy of the dopamine system in the basal ganglia.

The dopaminergic nigropallidal and nigrosubthalamic projections control the activity of the globus pallidus and subthalamic nucleus neurons in both normal and pathological conditions. Intrastriatal dopaminergic neurons increase substantially in animal models of Parkinson's disease. They contain GABA, display the ultrastructural features of interneurons and form axo-axonic synapses with putative cortical-like glutamatergic boutons. The local dendritic release of dopamine by neurons in the substantia nigra pars compacta and ventral tegmental also influences basal ganglia functions. Thus, the long-term belief that the effects of dopamine in the basal ganglia were solely mediated through the nigrostriatal system must be changed to take into account extrastriatal dopaminergic projections and intrastriatal dopaminergic neurons.

Animals↗
PubMed2000

GABA(B) and group I metabotropic glutamate receptors in the striatopallidal complex in primates.

Glutamate and GABA neurotransmission is mediated through various types of ionotropic and metabotropic receptors. In this review, we summarise some of our recent findings on the subcellular and subsynaptic localisation of GABA(B) and group I metabotropic glutamate receptors in the striatopallidal complex of monkeys. Polyclonal antibodies that specifically recognise GABA(B)R1, mGluR1a and mGluR5 receptor subtypes were used for immunoperoxidase and pre-embedding immunogold techniques at the light and electron microscope levels. Both subtypes of group I mGluRs were expressed postsynaptically in striatal projection neurons and interneurons where they aggregate perisynaptically at asymmetric glutamatergic synapses and symmetric dopaminergic synaptic junctions. Moreover, they are also strongly expressed in the main body of symmetric synapses established by putative intrastriatal GABAergic terminals. In the globus pallidus, both receptor subtypes are found postsynaptically in the core of striatopallidal GABAergic synapses and perisynaptically at subthalamopallidal glutamatergic synapses. Finally, extrasynaptic labelling was commonly seen in the globus pallidus and the striatum. Moderate to intense GABA(B)R1 immunoreactivity was observed in the striatopallidal complex. At the electron microscope level, GABA(B)R1 immunostaining was commonly found in neuronal cell bodies and dendrites. Many striatal dendritic spines also displayed GABA(B)R1 immunoreactivity. Moreover, GABA(B)R1-immunoreactive axons and axon terminals were frequently encountered. In the striatum, GABA(B)R1-immunoreactive boutons resembled terminals of cortical origin, while in the globus pallidus, subthalamic-like terminals were labelled. Pre-embedding immunogold data showed that postsynaptic GABA(B)R1 receptors are concentrated at extrasynaptic sites on dendrites, spines and somata in the striatopallidal complex, perisynaptically at asymmetric synapses and in the main body of symmetric striatopallidal synapses in the GPe and GPi. Consistent with the immunoperoxidase data, immunoparticles were found in the presynaptic grid of asymmetric synapses established by cortical- and subthalamic-like glutamatergic terminals. These findings indicate that both GABA and glutamate metabotropic receptors are located to subserve various modulatory functions of the synaptic transmission in the primate striatopallidal complex. Furthermore, their pattern of localisation raises issues about their roles and mechanisms of activation in normal and pathological conditions. Because of their 'modulatory' functions, these receptors are ideal targets for chronic drug therapies in neurodegenerative diseases such as Parkinson's disease.

Animals↗
PubMed2000

Improving screening for melanoma by measuring similarity to pre-classified images.

A new method that can dramatically improve the sensitivity and especially the specificity of skin naevi screening for melanoma by physicians is introduced. The method is based on measuring the similarity to previously classified naevi images. As more naevi are being classified, the power of the method is enhanced. Thus physicians can benefit from experience accumulated by others and the screening can be performed effectively by physicians with less experience.

Dysplastic Nevus Syndrome↗
PubMed1999

Group I metabotropic glutamate receptors at GABAergic synapses in monkeys.

Recent data showed that group I metabotropic glutamate receptors (mGluRs) are located perisynaptic to the postsynaptic specializations of asymmetric glutamatergic synapses in the cerebellum and hippocampus in rats. In the present study, we used immunogold labeling to elucidate the subsynaptic localization of group I mGluRs (mGluR1a and mGluR5) in the internal and external segments of the globus pallidus in monkeys. In contrast to hippocampal and cerebellar neurons, which receive massive glutamatergic inputs, dendrites of pallidal neurons are covered with GABAergic boutons from the striatum intermingled with a small proportion of glutamatergic terminals arising largely from the subthalamic nucleus. In line with previous data, mGluR1a and mGluR5 immunoreactivity was found at the edge of the postsynaptic specializations of asymmetric synapses established by subthalamic-like boutons in the monkey pallidum. However, a large proportion of gold particles were also seen in the main body of the postsynaptic specializations of symmetric synapses formed by striatal GABAergic terminals. These data raise questions about the possible sources of activation of these receptors and the potential roles of group I mGluRs in modulating GABAergic neurotransmission at striatopallidal synapses.

Animals↗
PubMed1999

CART peptide-immunoreactive neurones in the nucleus accumbens in monkeys: ultrastructural analysis, colocalization studies, and synaptic interactions with dopaminergic afferents.

Cocaine- and amphetamine-regulated transcript (CART) is a novel mRNA whose level of expression was found to be increased in the striatum after acute administration of psychomotor stimulants in rats. To define better the potential role of CART peptides in behavioural and physiologic changes induced by psychomotor stimulants, we analyzed the distribution, ultrastructural features, synaptic connectivity, and transmitter content of CART peptide-immunoreactive neurones in the nucleus accumbens in monkeys. Medium-sized CART peptide-immunoreactive neurones within a rich plexus of labelled varicosities were found mostly in the medial division of the shell of the nucleus accumbens in monkeys. At the electron microscope level, CART peptide immunoreactivity was exclusively associated with neuronal structures that included perikarya, dendrites, spines as well as nerve terminals packed with electron-lucent and dense-core vesicles. Most CART peptide-containing somata displayed the ultrastructural features of striatal output neurones. The majority of labelled terminals formed symmetric axodendritic synapses and displayed gamma-aminobutyric acid (GABA) immunoreactivity. CART peptide-immunoreactive somata were not immunoreactive for parvalbumin and somatostatin, two markers of striatal interneurones, nor for calbindin D-28k, a marker of a subpopulation of projection neurones. In double-immunostained sections, CART peptide-immunoreactive dendrites were found to be contacted by tyrosine hydroxylase-positive terminals which displayed the ultrastructural features of dopamine-containing boutons. These findings strongly suggest that CART peptides may be a cotransmitter with GABA in a subpopulation of projection neurones in the monkey accumbens. Furthermore, the fact that CART peptide-immunoreactive neurones receive direct synaptic inputs from dopaminergic afferents and are particularly abundant in the caudomedial division of the shell of the nucleus accumbens suggest that CART peptides might be involved in neuronal and behavioural changes that underlie addiction to psychomotor stimulants and feeding in primates.

Animals↗
PubMed1999

Similarity measurement method for the classification of architecturally differentiated images.

A similarity measurement method for the classification of architecturally differentiated image sections is described. The strength of the method is demonstrated by performing the complex task of assigning severity grading (Gleason grading) to histological slides of prostate cancer. As shown, all that is required to employ the method is a small set of preclassified images. The images can be real world images acquired by means of a camera, computer tomography, etc., or schematic drawings representing samples of different classes. The schematic option allows a quick test of the method for a particular classification problem.

Computers↗
PubMed1999

Thalamic inputs to striatal interneurons in monkeys: synaptic organization and co-localization of calcium binding proteins.

Recent studies indicate that extrinsic inputs from sensorimotor regions of the cerebral cortex and the centromedian intralaminar thalamic nucleus terminate preferentially upon specific subpopulations of striatal output neurons in monkeys. The objective of the present study was to verify whether this specificity of innervation also characterizes the synaptic interactions between thalamic inputs from the centromedian nucleus and the four major populations of striatal interneurons. This was achieved by double labelling techniques at the electron microscope level, combining the anterograde transport of biotinylated-dextran amine with the immunostaining for specific markers of striatal interneurons (somatostatin, parvalbumin, choline acetyltransferase and calretinin). Injections of biotinylated-dextran amine in the centromedian nucleus led to dense bands of anterograde labelling which, in double immunostained sections, largely overlapped with the four populations of interneurons in the post-commissural region of the putamen. In the electron microscope, biotinylated-dextran amine-containing terminals formed asymmetric axo-dendritic synapses with somatostatin-, parvalbumin-, and choline acetyltransferase-containing elements. However, synapses between anterogradely labelled terminals and calretinin-positive neurons were not found. In sections processed to localize biotinylated-dextran amine and parvalbumin or calretinin, double-labelled terminals (biotinylated-dextran amine/parvalbumin and biotinylated-dextran amine/calretinin), morphologically similar to thalamostriatal boutons, were found in the striatum indicating that calcium binding proteins may be expressed by thalamostriatal neurons. To test this possibility, we combined the retrograde transport of lectin-conjugated horseradish peroxidase from the putamen with parvalbumin and calretinin immunostaining and found that, indeed, most of the retrogradely labelled cells in the centromedian nucleus displayed parvalbumin and calretinin immunoreactivity. Moreover, co-localization studies revealed that calretinin and parvalbumin co-exist in single neurons of the centromedian nucleus. In conclusion, striatal interneurons immunoreactive for somatostatin, parvalbumin and choline acetyltransferase, but not those containing calretinin, receive strong inputs from the centromedian nucleus in monkeys. Moreover, our findings indicate that parvalbumin and calretinin co-exist in individual thalamostriatal neurons. In combination with our previous data, these results suggest that thalamic information may be conveyed to striatal projection neurons both, directly via excitatory synaptic inputs, or indirectly via striatal interneurons. The relative importance of those direct and indirect thalamic influences upon the activity of striatal output neurons remains to be established.

Animals↗
PubMed1999

Presynaptic kainate receptors in the monkey striatum.

Although kainate has long been known as a powerful axon-sparing neurotoxin, the localization and functions of kainate receptors in the CNS are largely unknown. In the present study we examined the distribution of kainate receptor subunits in the monkey striatum using kainate receptor subunits GluR6/7 and kainate receptor subunit KA2 subunit antibodies at the electron microscope level. We found that kainate receptor subunits GluR6/7 immunoreactivity is expressed not only in neuronal perikarya and dendritic processes, but also in a large population of terminals which form axospinous and axodendritic asymmetric synapses. The ultrastructural features of these terminals resembled those of glutamatergic corticostriatal boutons. In contrast, very few kainate receptor subunit KA2-containing terminals were encountered. Although the functions of these presynaptic kainate receptors remain to be established, the present data suggest the possibility that they are located to modulate the release of glutamate from cortical afferents in the monkey striatum, and that an abnormal regulation of these presynaptic receptors might be involved in the death of striatal neurons in Huntington's disease. Accordingly, recent findings demonstrated that the variance in the age of onset of Huntington's disease could be attributed to the genotype variation of kainate receptor subunit GluR6 in humans.

Animals↗
PubMed1998

Cat intraamygdaloid inhibitory network: ultrastructural organization of parvalbumin-immunoreactive elements.

Projection neurons of the basolateral (BL) amygdaloid complex are regulated by an intrinsic inhibitory network. To improve our understanding of this inhibitory circuit, we studied the synaptology of parvalbumin-immunopositive (PV+) elements as this calcium-binding protein is localized in a subpopulation of gamma-aminobutyric acid (GABA)-ergic interneurons. Two populations of PV+ cells were identified on the basis of soma shape (ovoid, type A vs. polygonal, type B). In the lateral and BL nuclei, the majority of boutons in contact with PV+ cells formed asymmetric synapses (types 1-3; 94%), whereas a minority (type 4, 6%) established symmetric synaptic contacts and resembled GABAergic terminals. In both nuclei, type B PV+ perikarya were more densely innervated than were type A neurons. However, the pattern of synaptic innervation of type B PV+ neurons differed in the two nuclei: in the lateral nucleus, they were almost exclusively innervated by a population of small, presumed excitatory terminals (type 1), whereas the four categories of terminals contributed more equally to their innervation in the BL nucleus. PV+ boutons belonged to a single category of terminals that was enriched with GABA and formed symmetric synapses mostly with the proximal part of PV neurons. The proportion of axosomatic synapses was significantly higher in the lateral nucleus than in the BL nucleus (33% vs. 18%). The reverse was true for the contacts with proximal dendrites (33% in the lateral nucleus vs. 46% in the BL nucleus). The remaining terminals formed synapses with distal dendrites (23-28%) and spines (8-12%). These results indicate that PV+ interneurons receive massive excitatory inputs and that PV+ terminals are strategically located to exert a powerful inhibitory control of amygdala neurons.

Amygdala↗
PubMed1998

CART peptides in the central control of feeding and interactions with neuropeptide Y.

While CART peptides have been implicated as novel, putative peptide neurotransmitters/cotransmitters, behavioral effects of these peptides have not yet been demonstrated. In this study, we show the first behavioral effect of CART peptides. I.c.v. administration of CART peptide fragments inhibits feeding in rats. Moreover, injection of an antibody to CART peptide 82-103 stimulates feeding, suggesting that endogenous CART peptides exert an inhibitory tone on feeding. Injection of CART peptide 82-103 five min before NPY reduces the increase in feeding caused by injection of NPY alone. Also, in light microscopic immunohistochemical studies, NPY-positive varicosities were observed around CART peptide-positive cell bodies in the paraventricular nucleus of the hypothalamus. These data suggest functional interactions between CART peptides and NPY. These results indicate that CART peptides play a role in the control of food intake by the brain.

Amino Acid Sequence↗
PubMed1998

Cocaine- and amphetamine-regulated transcript (CART) peptide immunoreactivity in myenteric plexus neurons of the rat ileum and co-localization with choline acetyltransferase.

Cocaine and amphetamine regulated transcript (CART) encodes a novel brain-enriched protein whose features are reminiscent of a neurotransmitter propeptide. We have now localized CART peptide(s) in the gastrointestinal tract by immunohistochemical methods. Polyclonal antisera raised to CART peptide 106-129 stained neuronal cell bodies and fibers in rat ileum myenteric plexus-longitudinal muscle tissue preparations. Electron microscopic analysis of thin sections showed immunopositive axon terminals in close apposition to CART-labelled and unlabelled neuronal cell bodies as well as to the longitudinal muscle. CART peptide-immunoreactive terminals contained numerous ovoid electron-lucent vesicles and a few dark-stained dense-core vesicles. Light microscopic double labelling studies revealed CART peptide immunoreactivity in a subpopulation of choline acetyltransferase (ChAT)-immunoreactive neurons. This combined light microscopic and ultrastructural examination of CART peptides in the gastrointestinal tract suggests a role of CART peptides as transmitters or neuromodulators in the peripheral nervous system.

Animals↗