Showing papers in "The Journal of Comparative Neurology in 1995"
TL;DR: This study identifies immunohistochemically the main subunit combinations expressed in the adult rat brain and allocates them to identified neurons, providing the basis for a functional analysis of GABAA‐receptor subtypes of known subunit composition and may open the way for unproved therapeutic approaches based on the development of subtype‐selective drugs.
Abstract: GABAA-receptors display an extensive structural heterogeneity based on the differential assembly of a family of at least 15 subunits (alpha 1-6, beta 1-3, gamma 1-3, delta, rho 1-2) into distinct heteromeric receptor complexes. The subunit composition of receptor subtypes is expected to determine their physiological properties and pharmacological profiles, thereby contributing to flexibility in signal transduction and allosteric modulation. In heterologous expression systems, functional receptors require a combination of alpha-, beta-, and gamma-subunit variants, the gamma 2-subunit being essential to convey a classical benzodiazepine site to the receptor. The subunit composition and stoichiometry of native GABAA-receptor subtypes remain unknown. The aim of this study was to identify immunohistochemically the main subunit combinations expressed in the adult rat brain and to allocate them to identified neurons. The regional and cellular distribution of seven major subunits (alpha 1, alpha 2, alpha 3, alpha 5, beta 2,3, gamma 2, delta) was visualized by immunoperoxidase staining with subunit-specific antibodies (the beta 2- and beta 3-subunits were covisualized with the monoclonal antibody bd-17). Putative receptor subtypes were identified on the basis of colocalization of subunits within individual neurons, as analyzed by confocal laser microscopy in double- and triple-immunofluorescence staining experiments. The results reveal an extraordinary heterogeneity in the distribution of GABAA-receptor subunits, as evidenced by abrupt changes in immunoreactivity along well-defined cytoarchitectonic boundaries and by pronounced differences in the cellular distribution of subunits among various types of neurons. Thus, functionally and morphologically diverse neurons were characterized by a distinct GABAA-receptor subunit repertoire. The multiple staining experiments identified 12 subunit combinations in defined neurons. The most prevalent combination was the triplet alpha 1/beta 2,3/gamma 2, detected in numerous cell types throughout the brain. An additional subunit (alpha 2, alpha 3, or delta) sometimes was associated with this triplet, pointing to the existence of receptors containing four subunits. The triplets alpha 2/beta 2,3/gamma 2, alpha 3/beta 2,3/gamma 2, and alpha 5/beta 2,3/gamma 2 were also identified in discrete cell populations. The prevalence of these seven combinations suggest that they represent major GABAA-receptor subtypes. Five combinations also apparently lacked the beta 2,3-subunits, including one devoid of gamma 2-subunit (alpha 1/alpha 2/gamma 2, alpha 2/gamma 2, alpha 3/gamma 2, alpha 2/alpha 3/gamma 2, alpha 2/alpha 5/delta).(ABSTRACT TRUNCATED AT 400 WORDS)
1,288 citations
TL;DR: This study has shown that the orbital and medial prefrontal cortex (OMPFC) is extensively connected with medial temporal and cingulate limbic structures, and the organization of these projections was defined in relation to architectonic areas within the OMPFC.
Abstract: Previous studies have shown that the orbital and medial prefrontal cortex (OMPFC) is extensively connected with medial temporal and cingulate limbic structures. In this study, the organization of these projections was defined in relation to architectonic areas within the OMPFC. All of the limbic structures were substantially connected with the following posterior and medial orbital areas: the posteromedial, medial, intermediate, and lateral agranular insular areas (Iapm, Iam, Iai, and Ial, respectively) and areas 11m, 13a, 13b, 14c and 14r. In contrast, lateral orbital areas 12o, 12m, and 12l and medial wall areas 24a,b and 32 were primarily connected with the amygdala, the temporal pole, and the cingulate cortex. Data were not obtained on the posteroventral medial wall. Three distinct projections were recognized from the basal amygdaloid nucleus: 1) The dorsal part projected to area 12l; 2) the ventromedial part projected to most areas in the posterior and medial orbital cortex except for area Iai, 12o, 13a, and 14c; and 3) the ventrolateral part projected to orbital areas 12o, Iai, 13a, 14c, and to the medial wall areas. The accessory basal and lateral amygdaloid nuclei projected most strongly to areas in the posterior and medial orbital cortex. The medial, anterior cortical, and central amygdaloid nuclei and the periamygdaloid cortex were connected with the posterior orbital areas. The projection from the hippocampus originated from the rostral subiculum and terminated in the medial orbital areas. The same region was reciprocally connected with the anteromedial nucleus of the thalamus, which received input from the rostral subiculum. The parahippocampal cortical areas (including the temporal polar, entorhinal, perirhinal, and posterior parahippocampal cortices) were primarily connected with posterior and medial orbital areas, with some projections to the dorsal part of the medial wall. The rostral cingulate cortex sent fibers to the medial wall, to the medial orbital areas, and to lateral areas 12o, 12r, and Iai. The posterior cingulate gyrus, including the caudomedial lobule, was especially strongly connected with area 11m.
1,285 citations
TL;DR: The surface morphology and cytoarchitecture of human cingulate cortex was evaluated in the brains of 27 neurologically intact individuals to provide structural underpinnings for interpreting functional imaging studies of the human medial surface.
Abstract: The surface morphology land cytoarchitecture of human cingulate cortex was evaluated in the brains of 27 neurologically intact individuals. Variations in surface features included a single cingulate sulcus (CS) with or without segmentation or double parallel sulci with or without segmentation. The single CS was deeper (9.7 ± 0.81 mm) than in cases with double parallel sulci (7.5 ± 0.48 mm). There were dimples parallel to the CS in anterior cingulate cortex (ACC) and anastomoses between the CS and the superior CS. Flat maps of the medial cortical surface were made in a two-stage reconstruction process and used to plot areas. The ACC is agranular and has a prominent layer V. Areas 33 and 25 have poor laminar differentiation, and there are three parts of area 24: area 24a adjacent to area 33 and partially within the callosal sulcus has homogeneous layers II and III, area 24b on the gyral surface has the most prominent layer Va of any cingulate area and distinct layers IIIa-b and IIIc, and area 24c in the ventral bank of the CS has thin layers II–III and no differentiation of layer V. There are four caudal divisions of area 24. Areas 24a′ and 24b′ have a thinner layer Va and layer III is thicker and less dense than in areas 24a and 24b. Area 24c′ is caudal to area 24c and has densely packed, large pyramids throughout layer V. Area 24c'g is caudal to area 24c′ and has the largest layer Vb pyramidal neurons in cingulate cortex. Area 32 is a cingulofrontal transition cortex with large layer IIIc pyramidal neurons and a dysgranular layer IV. Area 32′ is caudal to area 32 and has an indistinct layer IV, larger layer IIIc pyramids, and fewer neurons in layer Va. Posterior cingulate cortex has medial and lateral parts of area 29, a dysgranular area 30, and three divisions of area 23: area 23a has a thin layer IIIc and moderate-sized pyramids in layer Va, area 23b has large and prominent pyramids in layers IIIc and Va, and area 23c has the thinnest layers V and VI in cingulate cortex. Area 31 is the cinguloparietal transition area in the parasplenial lobules and has very large layer IIIc pyramids. Finally, variations in architecture between cases were assessed in neuron perikarya counts in area 23a. There was an age-related decrease in neuron density in layer IV (r = −0.63; ages 45–102), but not in other layers. These observations provide structural underpinnings for interpreting functional imaging studies of the human medial surface. © 1995 Wiley-Liss, Inc.
770 citations
TL;DR: Sensory and premotor inputs to the orbital and medial prefrontal cortex (OMPFC) were studied with retrograde axonal tracers with specific connections with visual‐, somatosensory‐, olfactory‐, gustatory‐, and visceral‐related structures.
Abstract: Sensory and premotor inputs to the orbital and medial prefrontal cortex (OMPFC) were studied with retrograde axonal tracers. Restricted areas of the lateral and posterior orbital cortex had specific connections with visual-, somatosensory-, olfactory-, gustatory-, and visceral-related structures. More medial areas received few direct sensory inputs. Within the lateral and posterior orbital cortex, area 12l received a substantial projection from visual areas in the inferior temporal cortex (TE). Area 12m received somatosensory input from face, digit, or forelimb regions in the opercular part of area 1-2, in area 7b, in the second somatosensory area (SII), and in the anterior infraparietal area (AIP). Areas 13m and 13l also received a projection from the opercular part of areas 1-2 and 3b. The posteromedial and lateral agranular insular areas (Iapm and Ial, respectively) received fibers from the ventral part of the parvicellular division of the ventroposterior medial nucleus of the thalamus (VPMpc) that may represent a visceral afferent system. The dorsal part of VPMpc projected to the adjacent gustatory cortex. These restricted inputs from several sensory modalities and the convergent corticocortical connections to orbital areas 13l and 13m suggest a network related to feeding. The OMPFC was also connected to premotor cortex in ventral area 6 (areas 6va and 6vb), in cingulate area 24c, and probably in the supplementary eye field. Area 6va projected to area 12m, whereas a region of area 6vb projected to area 13l. The region of the supplementary eye field projected to areas 12l, 12o, and 12r. Area Ial received fibers from area 24c. Lighter and more diffuse projections also reached wider areas of the OMPFC. For example, injections in several orbital areas labeled a few cells scattered through the anterior part of area TE and the superior temporal gyrus. There was also a projection to the intermediate agranular insular area (Iai) and to areas 13a and 12o from the apparently multimodal areas in the superior temporal sulcus and gyrus.
718 citations
TL;DR: Light and electron microscopic evidence indicates that some mGLUR5 immunoreactivity is located in presynaptic axon terminals, suggesting that mGluR5 may function as a Presynaptic receptor.
Abstract: The receptor mGluR5 is a metabotropic glutamate receptor with messenger RNA abundantly present throughout cortex, hippocampus, and caudate/putamen that is also coupled to phosphatidyl inositide hydrolysis and calcium mobilization. In this study, the distribution of mGluR5 was examined in rat brain by immunocytochemistry. The antibody utilized is highly specific and does not cross react with the most closely related other metabotropic glutamate receptor, as determined by Western blot analysis of nonneuronal cells transfected with metabotropic receptor coding sequences. The receptor mGluR5 is widely expressed with the highest density in olfactory bulb, caudate/putamen, lateral septum, cortex, and hippocampus, as confirmed with both immunocytochemistry and Western blot analysis. Electron microscopic studies in hippocampus and cortex indicate that the labeling is mostly on membranes of dendritic spines and shafts. Light and electron microscopic evidence indicates that some mGluR5 immunoreactivity is located in presynaptic axon terminals, suggesting that mGluR5 may function as a presynaptic receptor.
706 citations
TL;DR: The results of this study demonstrate that nervous which express these 5‐HT receptor subtypes are very widespread in the central nervous system, yet possess unique distributions with in the rat brain, which leads to the possibility that individual cells may express more than one 5‐ HT receptor subtype.
Abstract: Serotonin (5-HT) mediates its effects on neurons in the central nervous system through a number of different receptor types. To gain better insight as to the localization of 5-HT responsive cells, the distribution of cells expressing mRNAs encoding the three 5-HT receptor subtypes 1A, 1C, and 2 was examined in rat brain with in situ hybridization using cRNA probes. 5-HT1A receptor mRNA labeling was most pronounced in the olfactory bulb, anterior hippocampal rudiment, septum, hippocampus (dentate gyrus and layers CA1-3), entorhinal cortex, interpeduncular nucleus, and medullary raphe nuclei. 5-HT1C receptor mRNA labeling was the most abundant and widespread of the three 5-HT receptor subtypes examined. Hybridization signal was densest in the choroid plexus, anterior olfactory nucleus, olfactory tubercle, piriform cortex, septum, subiculum, entorhinal cortex, claustrum, accumbens nucleus, striatum, lateral amygdala, paratenial and paracentral thalamic nuclei, subthalamic nucleus, substantia nigra, and reticular cell groups. 5-HT2 receptor mRNA was localized to the olfactory bulb, anterior hippocampal rudiment, frontal cortex, piriform cortex, entorhinal cortex, claustrum, pontine nuclei, and cranial nerve motor nuclei including the oculomotor, trigeminal motor, facial, dorsal motor nucleus of the vagus, and hypoglossal nuclei. The distributions of mRNAs for the three different 5-HT receptor subtypes overlap with regions that bind various 5-HT receptor-selective ligands and are present in nearly all areas known to receive serotonergic innervation. The results of this study demonstrate that neurons which express these 5-HT receptor subtypes are very widespread in the central nervous system, yet possess unique distributions within the rat brain. Moreover, previously unreported regions of 5-HT receptor subtype expression were observed, particularly with the 5-HT2 receptor riboprobe in the brainstem. Finally, several brain areas contain multiple 5-HT receptor subtype mRNAs, which leads to the possibility that individual cells may express more than one 5-HT receptor subtype.
567 citations
TL;DR: Testing the ability of SC to enhance axonal regeneration in adult rat spinal cord by grafting SC‐seeded guidance channels into transected cords found purified populations of SC transplanted within channels promote both propriospinal and sensory axonal regenerate in the adult rat thoracic spinal cord.
Abstract: Schwann cells (SC) have been shown to promote regeneration in both the peripheral and central nervous systems. In this study we tested the ability of SC to enhance axonal regeneration in adult rat spinal cord by grafting SC-seeded guidance channels into transected cords. SC were purified in culture from adult inbred rat sciatic nerves, suspended in Matrigel, and seeded into semipermeable PAN/PVC channels (2.6 mm I.D. x 10 mm long) at a final density of 120 x 10(6) cells/ml. Channels filled with Matrigel alone served as controls. Adult isologous rat spinal cords were transected at the T8 level, and segments T9-T11 were removed. The rostral stump was inserted 1 mm into channels with capped distal ends. One month after grafting, a vascularized tissue cable was present within the channel in all animals. In SC-seeded channels (n = 14), a mean of 501 myelinated axons was found in the cable, and many axons extended 9-10 mm. Electron microscopy revealed typical SC ensheathment and myelination of axons with four times more unmyelinated than myelinated axons. Control channels (n = 8) contained fewer myelinated axons (mean = 71). When SC were prelabeled in culture with a nuclear dye, labeled nuclei were observed at 30 days, confirming SC survival. Astrocytes identified by glial fibrillary acidic protein staining did not migrate far into the cable, and prelabeled SC did not enter the cord. Lack of immunostaining for serotonin and dopamine beta-hydroxylase indicated that supraspinal axons did not regenerate into the cable. Fast Blue injections into the middle of the cable (n = 3) marked spinal cord interneurons (mean = 306) as far as nine segments rostral (25 mm, C7) extending axons into the graft; fewer dorsal root ganglion neurons were retrogradely labeled. In conclusion, purified populations of SC transplanted within channels promote both propriospinal and sensory axonal regeneration in the adult rat thoracic spinal cord.
566 citations
TL;DR: This study used Western blot analysis and immunohistochemistry to describe the biochemical characterization and anatomical distribution of the second, mitogen‐inducible form of this enzyme, COX 2 in the rat brain.
Abstract: Considerable debate exists regarding the cellular source of prostaglandins in the mammalian central nervous system (CNS). At least two forms of prostaglandin endoperoxide synthase, or cyclooxygenase (COX), the principal enzyme in the biosynthesis of these mediators, are known to exist. Both forms have been identified in the CNS, but only the distribution of COX 1 has been mapped in detail. In this study, we used Western blot analysis and immunohistochemistry to describe the biochemical characterization and anatomical distribution of the second, mitogen-inducible form of this enzyme, COX 2 in the rat brain. COX 2-like immunoreactive (COX 2-ir) staining occurred in dendrites and cell bodies of neurons, structures that are typically postsynaptic. It was noted in distinct portions of specific cortical laminae and subcortical nuclei. The distribution in the CNS was quite different from COX 1. COX 2-ir neurons were primarily observed in the cortex and allocortical structures, such as the hippocampal formation and amygdala. Within the amygdala, neurons were primarily observed in the caudal and posterior part of the deep and cortical nuclei. In the diencephalon, COX 2-ir cells were also observed in the paraventricular nucleus of the hypothalamus and in the nuclei of the anteroventral region surrounding the third ventricle, including the vascular organ of the lamina terminalis. COX 2-ir neurons were also observed in the subparafascicular nucleus, the medial zona incerta, and pretectal area. In the brainstem, COX 2-ir neurons were observed in the dorsal raphe nucleus, the nucleus of the brachium of the inferior colliculus, and in the region of the subcoeruleus. The distribution of COX 2-ir neurons in the CNS suggests that COX 2 may be involved in processing and integration of visceral and special sensory input and in elaboration of the autonomic, endocrine, and behavioral responses.
564 citations
TL;DR: Cortical and subcortical afferents to subdivisions of the medial frontal cortex in the rat were analyzed with fluorescent retrograde tracers and it was found that the number of retrogradely labeled cells was larger when the injection site was located in area IL.
Abstract: In order to compare the frontal cortex of rat and macaque monkey, cortical and subcortical afferents to subdivisions of the medial frontal cortex (MFC) in the rat were analyzed with fluorescent retrograde tracers. In addition to afferent inputs common to the whole MFC, each subdivision of the MFC has a specific pattern of afferent connections. The dorsally situated precentral medial area (PrCm) was the only area to receive inputs from the somatosensory cortex. The specific pattern of afferents common to the ventrally situated prelimbic (PL) and infralimbic (IL) areas included projections from the agranular insular cortex, the entorhinal and piriform cortices, the CA1-CA2 fields of the hippocampus, the subiculum, the endopiriform nucleus, the amygdalopiriform transition, the amygdalohippocampal area, the lateral tegmentum, and the parabrachial nucleus. In all these structures, the number of retrogradely labeled cells was larger when the injection site was located in area IL. The dorsal part of the anterior cingulate area (ACd) seemed to be connectionally intermediate between the adjacent areas PrCm and PL; it receives neither the somatosensory inputs characteristic of area PrCm nor the afferents characteristic of areas PL and IL, with the exception of the afferents from the caudal part of the retrosplenial cortex. A comparison of the pattern of afferent and efferent connections of the rat MFC with the pattern of macaque prefrontal cortex suggests that PrCm and ACd areas share some properties with the macaque premotor cortex, whereas PL and IL areas may have characteristics in common with the cingulate or with medial areas 24, 25, and 32 and with orbital areas 12, 13, and 14 of macaques.
514 citations
TL;DR: The common expression in both species of an IL‐1R in non‐neuronal elements highlights the possibility thatIL‐1‐mediated activation of CRF neurons may result from cytokine‐receptor interaction at vascular, and/or other barrier‐related, sites to trigger release of secondary signalling molecules in a position to interact with components of HPA control circuitry.
Abstract: Systemic interleukin-1 (IL-1) activates the hypothalamo-pituitary-adrenal (HPA) axis, an effect exerted through increased synthesis and secretion of corticotropin-releasing factor (CRF) by parvicellular neurosecretory neurons. The site(s) and mechanism(s) through which circulating IL-1 may access central systems governing HPA axis output remain obscure. To identify potential cellular targets for blood-borne IL-1, we analyzed the distribution of mRNA encoding the rat type 1 IL-1 receptor (IL-1R1) in rat brain. Regional ribonuclease protection assays detected a single protected fragment corresponding to the membrane-bound form of the IL-1R1 mRNA in all areas analyzed. In situ hybridization revealed labeling predominantly over barrier-related cells, including the leptomeninges, non-tanycytic portions of the ependyma, the choroid plexus, and vascular endothelium. Low to moderate levels of the IL-1R1 mRNA were detected in just a few neuronal cell groups, including the basolateral nucleus of the amygdala, the arcuate nucleus of the hypothalamus, the trigeminal and hypoglossal motor nuclei, and the area postrema. No specific labeling for IL-1R1 mRNA was detected over neurons that respond to intravenous IL-1 beta by induction of transcription factor Fos, including hypophysiotropic CRF cells and brainstem catecholamine neurons. Injection of IL-1 beta did, however, provoke induction of mRNA encoding the immediate-early gene, NGFI-B, but not c-fos, in two major loci of IL-1R1 expression, vascular endothelial cells, and the area postrema. Intravenous injection of IL-1 beta acutely down-regulated IL-1R1 mRNA in perivascular cells, but not in neuronal cell groups. These results suggest the parenchymal sites of IL-1R1 expression in rat to be distinct from those reported previously in mouse. The common expression in both species of an IL-1R in non-neuronal elements highlights the possibility that IL-1-mediated activation of CRF neurons may result from cytokine-receptor interaction at vascular, and/or other barrier-related, sites to trigger release of secondary signalling molecules in a position to interact with components of HPA control circuitry.
476 citations
TL;DR: The results show that the anterior PVT is ideally situated to relay circadian timing information from theSCN to brain areas involved in visceral and motivational aspects of behavior and to provide feedback regulation of the SCN.
Abstract: The paraventricular nucleus of the thalamus (PVT) receives input from all major components of the circadian timing system, including the suprachiasmatic nucleus (SCN), the intergeniculate leaflet and the retina. For a better understanding of the role of this nucleus in circadian timing, we examined the distribution of its efferent projections using the anterograde tracer Phaseolus vulgaris leucoagglutinin (PHA-L). The efferent projections of the PVT are loosely organized along its dorsal-ventral and anterior-posterior axes. The anterior PVT sends projections to the SCN; the dorsomedial and ventromedial hypothalamic nuclei; the lateral septum; the bed nucleus of the stria terminalis; the central and basomedial amygdaloid nuclei; the anterior olfactory nucleus; the olfactory tubercle; the nucleus accumbens; the infralimbic, piriform, and perirhinal cortices; the ventral subiculum; and the endopiriform nucleus. A small PHA-L injection, restricted to the ventral portion of the anterior PVT, produces a similar pattern of labeling, except for a marked decrease in the number of labeled fibers in the hypothalamus, cortex, and lateral septum and an increase in labeling in the endopiriform nucleus and basolateral amygdaloid nucleus. The posterior PVT has a more limited efferent distribution than the anterior PVT, terminating in the anterior olfactory nucleus; the olfactory tubercle; the nucleus accumbens; and the central, basolateral, and basomedial nuclei of the amygdala. Our results show that the anterior PVT is ideally situated to relay circadian timing information from the SCN to brain areas involved in visceral and motivational aspects of behavior and to provide feedback regulation of the SCN.
TL;DR: The retinal ganglion cells giving rise to retinohypothalamic projections in the rat were identified using retrograde transport of horseradish peroxidase or Fluoro Gold injected into the suprachiasmatic nucleus (SCN), and using transneuronal transport of the Bartha strain of the swine herpesvirus.
Abstract: The retinal ganglion cells giving rise to retinohypothalamic projections in the rat were identified using retrograde transport of horseradish peroxidase (HRP) or FluoroGold injected into the suprachiasmatic nucleus (SCN), and using transneuronal transport of the Bartha strain of the swine herpesvirus (PRV-Bartha). When PRV-Bartha is injected into one eye, it is taken up by retinal ganglion cells, replicated, transported to axon terminals in the SCN, and released. There the virus may take one, or both, of two paths to retinal ganglion cells in the contralateral eye: 1) uptake by SCN neurons, replication, and release from the neurons with uptake and retrograde transport in retinal afferents originating in the contralateral retina; 2) transneuronal passage through axo-axonic appositions between retinal afferents in the SCN with subsequent retrograde transport of virus to the contralateral retina. The ganglion cells thus labeled are a homogeneous population of small neurons (mean diameter, 12.8 +/- 2.2 microns and mean area, 81.8 +/- 21.8 microns 2) with sparsely branching dendrites that are widely distributed over the retina. This population is best identified when virus labeling of retinal projections in areas beyond the hypothalamus is eliminated by lateral geniculate lesions that transect the optic tract at its entry into the geniculate complex. The same population is labeled with retrograde tracers but, with both HRP and FluoroGold, other ganglion cells are labeled, presumably from uptake by fibers of passage, indicating that the virus is a more reliable marker for ganglion cells giving rise to retinohypothalamic projections. The ganglion cells identified correspond to a subset of type III, or W, cells.
TL;DR: Through the reticular formation, ventral tegmentum, raphe nuclei, and dorsal tegineritum, GAD‐positive cells were codistributed with larger cells, which included neurons immunostained on adjacent sections for glutamate, tyrosine hydroxylase (TH), serotonin, or choline acetyltransferase (ChAT).
Abstract: The present study was undertaken to determine the frequency and distribution of GABAergic neurons within the rat pontomesencephalic tegmentum and the relationship of GABAergic cells to cholinergic and other tegmental neurons projecting to the hypothalamus In sections immunostained for glutamic acid decarboxylase (GAD), large numbers of small GAD-positive neurons (approximately 50,000 cells) were distributed through the tegmentum and associated with a high density of GAD-positive varicosities surrounding both GAD-positive and GAD-negative cells Through the reticular formation, ventral tegmentum, raphe nuclei, and dorsal tegmentum, GAD-positive cells were codistributed with larger cells, which included neurons immunostained on adjacent sections for glutamate, tyrosine hydroxylase (TH), serotonin, or choline acetyltransferase (ChAT) In sections dual-immunostained for GAD and ChAT, GABAergic neurons were seen to be intermingled with less numerous cholinergic cells (approximately 2,600 GAD+ to approximately 1,400 ChAT+ cells in the laterodorsal tegmental nucleus, LDTg) Retrograde transport of cholera toxin (CT) was examined from the posterior lateral hypothalamus, where a major population of cortically projecting neurons are located A small number of GABAergic cells were retrogradely labeled, representing a small percentage of all the GABAergic neurons (approximately 1%) and of all the hypothalamically projecting neurons (approximately 6%) in the tegmentum The double-labeled GAD+/CT+ cells were commonly found ipsilaterally within 1) the deep mesencephalic reticular field, codistributed with putative glutamatergic projection neurons; 2) the ventral tegmental area, substantia nigra compacta, and retrorubral field, codistributed with dopaminergic projection neurons; 3) dorsal raphe, codistributed with serotonergic projection neurons; and 4) laterodorsal and pedunculopontine tegmental nuclei, codistributed with and in similar proportion to cholinergic projection cells (20-30% in LDTg) Acting as both projection and local neurons, the pontomesencephalic GABAergic cells would have the capacity to modulate the influence of the "ascending reticular activating system" and its chemically specific constituents upon cortical activation
TL;DR: These studies identified distinctive dendritic branching patterns, in the stratum radiatum and stratum lacunosum moleculare, which clearly distinguished CA3 from CAl neurons.
Abstract: The three dimensional organization of the dendritic trees of pyramidal cells in the rat hippocampus was investigated using intracellular injection of horseradish peroxidase in the in vitro hippocampal slice preparation and computer-aided reconstruction. The total dendritic length, dendritic length in each of the hippocampal laminae, and the number of dendritic branches were measured in 20 CAl pyramidal cells, 7 neurons in CA2 and 20 CA3 pyramidal cells. The total dendritic length of CA3 pyramidal cells varied in a consistent fashion depending on their position within the field. Cells located close to the dentate gyrus had the smallest dendritic trees which averaged 9,300 μm in total length. Cells in the distal part of CA3 (near CA2) had the largest dendritic trees, averaging 15,800 μm. The CA2 field contained cells which resembled CA3 pyramidal cells in most respects except for the absence of thorny excrescences on their proximal dendrites. There were also smaller pyramidal cells that resembled CAl neurons. CAl pyramidal cells tended to be more homogeneous. Pyramidal neurons throughout the transverse extent of CAl had a total dendritic length on the order of 13,500 μm. The quantitative analysis of the laminar distribution of dendrites demonstrated that the stratum oriens and stratum radiatum contained significant portions of the pyramidal cell dendritic trees. In CA3, for example, 42–51% of the total dendritic length was located in stratum oriens; about 34% of the dendritic tree was located in stratum radiatum. The amount of dendritic length in stratum lacunosum-moleculare of CA3 varied depending on the location of the cell. Many CA3 cells located within the limbs of the dentate gyrus, for example, had no dendrites extending into stratum lacunosum-moleculare whereas those located distally in CA3 had about the same percentage of their dendritic tree in stratum lacunosum-moleculare as in stratum radiatum. In CAl, nearly half of the dendritic length was located in stratum radiatum, 34% was in stratum oriens and 18% was in stratum lacunosum-moleculare. These studies identified distinctive dendritic branching patterns, in the stratum radiatum and stratum lacunosum moleculare, which clearly distinguished CA3 from CAl neurons. © Wiley-Liss, Inc.
TL;DR: The intrinsic connections identified in this study differ from the local circuits of corresponding layers reported for primary visual cortex; the unique intrinsic wiring diagram of the prefrontal cortex may be related to its specialized cognitive and mnemonic functions.
Abstract: Intrinsic connections are likely to play important roles in cognitive information processing in the prefrontal association cortex. To gain insight into the organization of these circuits, intracortical connections of major laminar and sublaminar divisions were retrogradely labeled in Walker's area 9 and 46 in rhesus monkeys by using cholera toxin (B-subunit) conjugated to colloidal gold. Microinjections placed within particular cortical laminae produced unique patterns of retrograde labeling. Injections in layers II/III yielded labeling which was laterally widespread (2-7 mm) in supragranular layers, and more narrowly focused, i.e., conforming to a column, in layers IV-VI. In contrast, local circuits associated with layers IV and Vb displayed a regular, cylindrical organization, whereas intrinsic connections of layer Va were laterally extensive (3-5 mm) in layers III and Va. Finally, injections in layer VI gave rise to a narrow column of cell labeling traversing all layers, augmented by laterally extensive labeling (approximately 7 mm) in layer VI. The intrinsic connections of the prefrontal cortex were arrayed within mediolaterally elongated stripes which were often distributed asymmetrically in either the medial or lateral direction. In addition, labeled cells within these mediolaterally oriented fields were frequently grouped within discrete clusters or narrow bands. The intrinsic connections identified in this study differ from the local circuits of corresponding layers reported for primary visual cortex; the unique intrinsic wiring diagram of the prefrontal cortex may be related to its specialized cognitive and mnemonic functions.
TL;DR: The results suggest that GDNF can maintain the dopaminergic neuronal phenotype in a number of nigral neurons following a unilateral nigrostriatal lesion in the rat.
Abstract: Glial cell-lined derived neurotrophic factor (GDNF) has been shown to promote survival of developing mesencephalic dopaminergic neurons in vitro. In order to determine if there is a positive effect of GDNF on injured adult midbrain dopaminergic neurons in situ, we have carried out experiments in which a single dose of GDNF was injected into the substantia nigra following a unilateral lesion of the nigrostriatal system. Rats were unilaterally lesioned by a single stereotaxic injection of 6-hydroxydopamine (6-OHDA; 9 micrograms/4 microliters normal saline with 0.02% ascorbate) into the medial forebrain bundle and tested weekly for apomorphine-induced (0.05 mg/kg s.c.) contralateral rotation behavior. Rats that manifested > 300 turns/hour received a nigral injection of 100 micrograms GDNF, or cytochrome C as a control, 4 weeks following the 6-OHDA lesion. Rotation behavior was quantified weekly for 5 weeks after GDNF. Rats were subsequently anesthetized, transcardially perfused, and processed for tyrosine hydroxylase immunohistochemistry. It was found that 100 micrograms GDNF decreased apomorphine-induced rotational behavior by more than 85%. Immunohistochemical studies revealed that tyrosine hydroxylase immunoreactivity was equally reduced in the striatum ipsilateral to the lesion in both cytochrome C and GDNF-injected animals. In contrast, large increments in tyrosine hydroxylase immunoreactivity were observed in the substantia nigra of animals treated with 100 micrograms of GDNF, with a significant increase in numbers of tyrosine hydroxylase-immunoreactive cell bodies and neurites as well as a small increase in the cell body area of these neurons. The results suggest that GDNF can maintain the dopaminergic neuronal phenotype in a number of nigral neurons following a unilateral nigrostriatal lesion in the rat.
TL;DR: Results show that rabies virus is a very efficient transneuronal tracer, and provide a new insight into the organization of cortical and subcortical higher order neurons that mediate descending control of tongue movements indirectly via hypoglossal‐projecting neurons.
Abstract: The specificity of transneuronal transfer of rabies virus [challenge virus standard (CVS) strain] was evaluated in a well-characterized neuronal network, i.e., retrograde infection of hypoglossal motoneurons and transneuronal transfer to connected (second-order) brainstem neurons. The distribution of the virus in the central nervous system was studied immunohistochemically at sequential intervals after unilateral inoculation into the hypoglossal nerve. The extent of transneuronal transfer of rabies virus was strictly time dependent and was distinguished in five stages. At 1 day postinoculation, labelling involved only hypoglossal motoneurons (stage 1). Retrograde transneuronal transfer occurred from 2.0-2.5 days postinoculation (stage 2). In stages 2-4, different groups of second-order neurons were labelled sequentially, depending on the strength of their input to the hypoglossal nucleus. In stages 4 and 5, labelling extended to several cortical and subcortical cell groups, which can be regarded as higher order because they are known to control tongue movements and/or to provide input to hypoglossal-projecting cell groups. The pattern of transneuronal transfer of rabies virus resembles that of alpha-herpesviruses with regard to the nonsynchronous labelling of different groups of second-order neurons and the transfer to higher order neurons. In striking contrast to alpha-herpesviruses, the transneuronal transfer of rabies is not accompanied by neuronal degeneration. Moreover, local spread of rabies from infected neurons and axons to adjoining glial cells, neurons, or fibers of passage does not occur. The results show that rabies virus is a very efficient transneuronal tracer. Results also provide a new insight into the organization of cortical and subcortical higher order neurons that mediate descending control of tongue movements indirectly via hypoglossal-projecting neurons.
TL;DR: This study has used antibodies to TrkA, in conjunction with cell biological markers that show a restricted distribution in the DRG, to further characterize subsets of DRG neurons that are dependent upon NGF, and suggests that TrKA‐expressing and non‐TrkA‐ expressing small neurons compose functionally distinct populations ofDRG neurons.
Abstract: Investigations into the biological actions of nerve growth factor (NGF) have shown that dorsal root ganglion (DRG) neurons subserving nociception require NGF for survival and maintenance of phenotype. This discovery suggests that the signaling NGF receptor, TrkA, can be used as a marker for nociceptive neurons. In this study, we have used antibodies to TrkA, in conjunction with cell biological markers that show a restricted distribution in the DRG, to further characterize subsets of DRG neurons that are dependent upon NGF. Staining for TrkA labeled small and medium-sized neurons that composed 47% of all neurons in thoracic ganglia. Double-labeling with antibodies to the high molecular weight neurofilament protein (NFH), a marker for neurons with myelinated axons, demonstrated that TrkA staining is found in only a small subset of myelinated neurons. Surprisingly, many DRG neurons were not labeled by either TrkA or NFH. These neurons had small soma areas, contained the intermediate filament protein peripherin, and were labeled by the lectin BSI, identifying them as neurons likely to have unmyelinated axons. In addition, small TrkA-negative neurons were extensively labeled by antibodies to the intermediate filament protein alpha-internexin, the delta isoform of protein kinase C, and by the BSI isolectin BSI-B4. In order to assess the potential functions of TrkA-negative small neurons, we examined their projections to the dorsal horn of the spinal cord. TrkA-immunoreactivity in the spinal cord was restricted to lamina I and the outer region of lamina II (IIo), similar to staining for calcitonin gene-related peptide. In contrast, the central projections of TrkA-negative neurons, as visualized by BSI-B4 staining, were particularly dense in lamina IIi. Our results suggest that TrkA-expressing and non-TrkA-expressing small neurons compose functionally distinct populations of DRG neurons.
TL;DR: The density and laterality of labeling in the medulla varied between cases independently from that in the pons and mesencephalon, suggesting that the lamina I projections to these regions may originate from different subsets of neurons.
Abstract: The distribution of terminal projections in the brainstem from lamina I neurons in the spinal dorsal horn was investigated with the anterograde tracer Phaseolus vulgaris–leucoagglutinin in the cat and the cynomolgus monkey. Iontophoretic injections made with physiological guidance were restricted to lamina I or to laminae I–III in the cervical (C6–8) or lumbar (L6–7) enlargement. The distribution of terminal labeling was essentially identical in the cat and the monkey, although consistently of greater intensity in the monkey. Terminations were observed in the solitary nucleus, the dorsomedial medullary reticular formation, the entire rostrocaudal extent of the ventrolateral medulla, the locus coeruleus, the subcoerulear region and the Kolliker–Fuse nucleus, the lateral and medial portions of the parabrachial nucleus, the cuneiform nucleus, the ventrolateral and lateral portions of the periaqueductal gray, and the intercollicular nucleus. Lamina I terminations were generally bilateral in the medulla but more dense contralaterally in the pons and mesencephalon. The density and laterality of labeling in the medulla varied between cases independently from that in the pons and mesencephalon, suggesting that the lamina I projections to these regions may originate from different subsets of neurons. A clear topographic organization was observed only in the lateral column of the periaqueductal gray, where lumbar lamina I terminations were found caudal to cervical terminations.
These observations indicate that spinal lamina I neurons project to a variety of brainstem sites involved in autonomic (cardiovascular, respiratory) and homeostatic processing and the control of behavioral state. These projections provide an afferent substrate for spino-bulbo-spinal somatoautonomic reflex arcs activated by nociceptive, thermoreceptive activity and for a spino-bulbo-hypothalamic relay of such activity by cells in the caudal ventrolateral medulla. These observations support the general concept that lamina I projections distribute modality-selective sensory information relevant to the physiological status and maintenance of the tissues and organs of the entire organism. © 1995 Wiley-Liss, Inc.
TL;DR: Dense iDAT was observed in patterns consistent with neural processes and terminals in the striatum, nucleus accumbens, olfactory tubercle, nigrostriatal bundle, and lateral habenula, and specificity of immunostaining was supported by agreement of the results.
Abstract: The dopamine transporter (DAT) is a primary site for the action of cocaine in inducing euphoria. Its action is necessary for the selectivities of dopaminergic neurotoxins that provide the best current experimental models of Parkinson's disease. In the present report, rat dopamine transporter-like immunoreactivity (iDAT) was assessed by immunohistochemistry using newly developed polyclonal antisera raised against conjugated peptides corresponding to sequences found in the dopamine transporter's carboxy- and amino-termini. Dense iDAT was observed in patterns consistent with neural processes and terminals in the striatum, nucleus accumbens, olfactory tubercle, nigrostriatal bundle, and lateral habenula. Perikarya in the substantia nigra pars compacta were immunostained with moderate intensity using one of two immunohistochemical methods, while scattered ventral tegmental area perikarya were stained with somewhat less intensity. Immunoreactive neuronal processes with axonal and dendritic morphologies were stained in the substantia nigra and the paranigral and parabrachialis pigmentosus nuclei of the ventral tegmental area, while sparser processes were noted more medially in the ventral tegmental area. Neuronal processes were found in several laminae in the cingulate cortex, with notable fiber densities in the superficial aspects of lamina I and laminae II/III. The intensities of immunoreactivities in striatum and cerebral cortex were dramatically attenuated ipsilateral to nigrostriatal bundle 6-hydroxydopamine lesions. Specificity of immunostaining was supported by agreement of the results using sera directed against two distinct DAT segments, studies with preimmune and preadsorbed sera and studies of the extracted protein. These antisera identify and reveal details of the distribution of DAT immunoreactivity in rat brain and display variations in levels of DAT expression of likely functional significance.
TL;DR: Although ganglia have been used for classical assays of neurotrophin action, knowledge is incomplete regarding the spatial arrangements through which neurotrophins are delivered to responsive cells within the ganglia and their attached nerve trunks.
Abstract: Nerve growth factor promotes the survival of populations of sensory and sympathetic neurons. Although ganglia have been used for classical assays of neurotrophin action, knowledge is incomplete regarding the spatial arrangements through which neurotrophins are delivered to responsive cells within the ganglia and their attached nerve trunks. Whereas populations of ganglionic neurons may be capable of responding to a particular neurotrophin in vitro, the spectrum of receptor components and neurotrophins expressed by the various neuronal and nonneuronal cells comprising the ganglia in adult rats remains to be elucidated in vivo. Brain-derived neurotrophic factor (BDNF) mRNA was expressed by a population of small to medium sized neurons in all sensory ganglia except in the mesencephalic nucleus of the trigeminal nerve. Interestingly, BDNF immunoreactivity was detected in a more widespread population of neurons of these ganglia, as well as in scattered satellite cells of both sensory and sympathetic ganglia. These nonneuronal cells also expressed mRNA encoding a truncated form of the BDNF receptor, trkBtrunc, and full-length transcripts of trkB appeared to be confined to neuronal populations. Several other components of neurotrophin receptors (low-affinity neurotrophin receptor, trk, and trkC) were prominently expressed by different populations of neuronal cells in sympathetic and sensory ganglia, but they were not detected in nonneuronal cells. Neither nerve growth factor nor neurotrophin-3 mRNAs were detected in these ganglia. Unexpectedly, BDNF and trkBtrunc expression was detected in oligodendrocytes myelinating the central processes of sensory neurons. Schwann cells did not express detectable quantities of either entity, thereby establishing a dramatic boundary delineated by neurotrophin/neurotrophin receptor expression that coincided with the interface between the oligodendroglia of the central nervous system (CNS) and Schwann cells of the peripheral nervous system (PNS). Localization of BDNF expression to an additional population of nonneuronal cells--satellite cells within sensory and sympathetic ganglia--suggest a more extensive role for neurotrophic factors than originally encompassed by the target-derived neurotrophic-factor-concept paradigm. These data support the hypothesis of a possible autocrine or paracrine trophic interaction between populations of neuronal and nonneuronal cells in the peripheral nervous system. BDNF expression in oligodendrocytes but not in Schwann cells at the CNS/PNS junction may provide an additional means of maintaining cell-appropriate connections in the nervous system.
TL;DR: Dopamine afferents provide direct synaptic inputs to GABA local circuit neurons in a consistent fashion across cortical regions and species, indicating that dopamine's cellular actions involve direct as well as modulatory effects on both GABA interneurons and pyramidal projection neurons.
Abstract: Dopamine afferents to the cortex regulate the excitability of pyramidal neurons via a direct synaptic input. However, it has not been established whether dopamine also modulates pyramidal cell activity indirectly through synapses on γ-aminobutyric acid (GABA) interneurons, and whether such inputs differ across cortical regions and species. We sought to address these issues by an immunocytochemical electron microscopic approach that combined peroxidase staining for dopamine or tyrosine hydroxylase (TH) with a pre-embedding gold-silver marker for GABA. In the deep layers of the rat prefrontal cortex and in the superficial layers of the monkey prefrontal and primary motor cortices, terminal varicosities immunoreactive for dopamine or TH formed primarily thin, symmetric synapses on distal dendrites. Both GABA-immunoreactive dendrites as well as unlabeled spines and dendrites were contacted by dopamine- or TH-immunoteactive terminals. Synaptic specializations were detected at some, but not all of these contacts. The relative frequency of these appositional and synaptic contacts did not appear to differ between the rat and monkey prefrontal cortex, or between the monkey prefrontal and motor cortices. Across regions and species, labeled and unlabeled targets of dopamine- or TH-positive terminals received additional synaptic input from unlabeled, and occasionally GABA-immunoreactive terminals. Close appositions between dopamine- or TH immunoreactive and GABA-positive terminals were observed only rarely. These findings indicate that dopamine afferents provide direct synaptic inputs to GABA local circuit neurons in a consistent fashion across cortical regions and species. Thus, dopamine's cellular actions involve direct as well as modulatory effects on both GABA interneurons and pyramidal projection neurons. © 1995 Wiley-Liss, Inc.
TL;DR: Amaral et al. as discussed by the authors investigated the cytoarchitectonic features of the human entorhinal cortex by using as a base their previous study (D.G. Amaral, R. Insausti, and W.M. Cowan [1987] J. Comp. Neurol. 264:326-355).
Abstract: The entorhinal cortex of man is in the medial aspect of the temporal lobe. As in other mammalian species, it constitutes an essential component of the hippocampal formation and the route through which the neocortex interacts with the hippocampus. The importance of knowing its architecture in detail arises from the possibility of extrapolating it to experimental findings, notably in the nonhuman primate. We have investigated the cytoarchitectonic features of the human entorhinal cortex by using as a base our previous study (D.G. Amaral, R. Insausti, and W.M. Cowan [1987] J. Comp. Neurol. 264:326-355) of the nonhuman primate entorhinal cortex. We prepared serial sections of the temporal lobe from 35 normal brains. Thionin- and myelin-stained series were made of all cases. Sections spaced 500 microns apart through the full rostrocaudal extent of the entorhinal cortex were analyzed. The human entorhinal cortex is made up of six layers, of which layer IV does not appear throughout all subfields of the entorhinal cortex. The overall appearance resembles that of the adjacent neocortex in lateral and caudal portions. In harmony with general structural principles in the nonhuman primate entorhinal cortex, our analysis supports the partitioning of the human entorhinal cortex into eight different subfields. (1) The olfactory subfield (EO), the rostralmost field, is little laminated. (2) The lateral rostral subfield (ELr), laterally located, merges with the laterally adjacent perirhinal cortex. (3) The rostral subfield (ER) is between EO and ELr, with better differentiation of layers II and III than EO. (4) The medial intermediate subfield (EMI) is located at the medial border. (5) The intermediate field (EI) is a lateral continuation of EMI; lamina dissecans (layer IV) can be best appreciated in this field. (6) The lateral caudal subfield (ELc) laterally borders on EI as a continuation of ELr. (7) The caudal subfield (EC) lies caudal to the beginning of the hippocampal fissure, with a distinctive, clear space (Vc) between layers V and VI. (8) The caudal limiting field (ECL) forms the caudal termination of the entorhinal cortex. Thus our parcellation of the entorhinal cortex in man is largely parallel to that arrived at in the monkey. This close homology provides a rational basis for the application to clinical problems of anatomical and functional information obtained in experimental work in nonhuman primates.
TL;DR: Observations indicate that the spindle cells of the human cingulate cortex represent a morphological subpopulation of pyramidal neurons whose restricted distribution may be associated with functionally distinct areas.
Abstract: The human anterior cingulate cortex is distinguished by the presence of an unusual cell type, a large spindle neuron in layer Vb. This cell has been noted numerous times in the historical literature but has not been studied with modern neuroanatomic techniques. For instance, details regarding the neuronal class to which these cells belong and regarding their precise distribution along both ventrodorsal and anteroposterior axes of the cingulate gyrus are still lacking. In the present study, morphological features and the anatomic distribution of this cell type were studied using computer-assisted mapping and immunocytochemical techniques. Spindle neurons are restricted to the subfields of the anterior cingulate cortex (Brodmann's area 24), exhibiting a greater density in anterior portions of this area than in posterior portions, and tapering off in the transition zone between anterior and posterior cingulate cortex. Furthermore, a majority of the spindle cells at any level is located in subarea 24b on the gyral surface. Immunocytochemical analysis revealed that the neurofilament protein triple was present in a large percentage of these neurons and that they did not contain calcium-binding proteins. Injections of the carbocyanine dye DiI into the cingulum bundle revealed that these cells are projection neurons. Finally, spindle cells were consistently affected in Alzheimer's disease cases, with an overall loss of about 60%. Taken together, these observations indicate that the spindle cells of the human cingulate cortex represent a morphological subpopulation of pyramidal neurons whose restricted distribution may be associated with functionally distinct areas.
TL;DR: It is found that a large continuous expanse of the outer pallium projects to the striatum of the basal ganglia in pigeons, termed by us the pallium externum (PE).
Abstract: Birds have well-developed basal ganglia within the telencephalon, including a striatum consisting of the medially located lobus parolfactorius (LPO) and the laterally located paleostriatum augmentatum (PA), Relatively little is known, however, about the extent and organization of the telencephalic “cortical” input to the avian basal ganglia (i. e., the avian “corticostriatal” projection system). Using retrograde and anterograde neuroanatomical pathway tracers to address this issue, we found that a large continuous expanse of the outer pallium projects to the striatum of the basal ganglia in pigeons. This expanse includes the Wulst and archistriatum as well as the entire outer rind of the pallium intervening between Wulst and archistriatum, termed by us the pallium externum (PE). In addition, the caudolateral neostriatum (NCL), pyriform cortex, and hippocampal complex also give rise to striatal projections in pigeon. A restricted number of these pallial regions (such as the “limbic” NCL, pyriform cortex, and ventral/caudal parts of the archistriatum) project to such ventral striatal structures as the olfactory tubercle (TO), nucleus accumbens (Ac), and bed nucleus of the stria terminalis (BNST). Such “limbic” pallial areas also project to medialmost LPO and lateralmost PA, while the hyperstriatum accessorium portion of the Wulst, the PE, and the dorsal parts of the archistriatum were found to project primarily to the remainder of LPO (the lateral two-thirds) and PA (the medial four-fifths).
The available evidence indicates that the diverse pallial regions projecting to the striatum in birds, as in mammals, are parts of higher order sensory or motor systems. The extensive corticostriatal system in both birds and mammals appears to include two types of pallial neurons: (1) those that project to both striatum and brainstem (i. e., those in the Wulst and the archistriatum) and (2) those that project to striatum but not to brainstem (i. e., those in the PE). The lack of extensive corticostriatal projections from either type of neuron in anamniotes suggests that the anamniote-amniote evolutionary transition was marked by the emergence of the corticostriatal projection system as a prominent source of sensory and motor information for the striatum, possibly facilitating the role of the basal ganglia in movement control. © 1995 Wiley-Liss, Inc.
TL;DR: The present study characterized the projections of theAnterodorsal (AD) and the anteroventral (AV) thalamic nuclei to the limbic cortex and found that both AD and AV project to the full extent of the retrosplenial granular cortex in a topographic pattern.
Abstract: The present study characterized the projections of the anterodorsal (AD) and the anteroventral (AV) thalamic nuclei to the limbic cortex. Both AD and AV project to the full extent of the retrosplenial granular cortex in a topographic pattern. Neurons in caudal parts of both nuclei project to rostral retrosplenial cortex, and neurons in rostral parts of both nuclei project to caudal retrosplenial cortex. Within AV, the magnocellular neurons project primarily to the retrosplenial granular a cortex, whereas the parvicellular neurons project mainly to the retrosplenial granular b cortex. AD projections to retrosplenial cortex terminate in very different patterns than do AV projections: The AD projection terminates with equal density in layers I, III, and IV of the retrosplenial granular cortex, whereas, in contrast, the AV projections terminate very densely in layer Ia and less densely in layer IV. Further, both AD and AV project densely to the postsubicular, presubicular, and parasubicular cortices and lightly to the entorhinal (only the most caudal part) cortex and to the subiculum proper (only the most septal part). Rostral parts of AD project equally to all three subicular cortices, whereas neurons in caudal AD project primarily to the postsubicular cortex. Compared to AD, neurons in AV have a less extensive projection to the subicular cortex, and this projection terminates primarily in the postsubicular and presubicular cortices. Further, the AD projection terminates in layers I, II/III, and V of postsubiculum, whereas the AV projection terminates only in layers I and V.
TL;DR: Cortical connections between various body representations in areas 3b and 1 and lateral parietal cortex were examined in 18 macaque monkeys and labeled regions include the second somatosensory area, retroinsular area, and granular insula.
Abstract: Cortical connections between various body representations in areas 3b and 1 and lateral parietal cortex were examined in 18 macaque monkeys. We injected tracers (Fast Blue, Diamidino Yellow, Horseradish Peroxidase, and Rhodamine Dextran), alone or in combination, into closely related cutaneous responsive sites, e. g., adjacent digits. Separated patches of labeling were found across the parietal operculum and insula for all injected locations. On the basis of cytoarchitectural criteria, the labeled regions include the second somatosensory area (SH), retroinsular area (Ri) and granular insula (Ig). Assuming the connections are homotopical from physiologically identified body representations in primary somatosensory cortex, the labeling patterns in SII include complete anterior and posterior body maps. The orientation of the body is erect in the posterior and supine in the anterior SII region. Area 3b has greater density of connections with anterior SIL The maps are mirror images aligned along the distal extremities. The anterior-posterior (A-P) length of the “SII region” exceeds 7 mm; it extends in the coronal plane from the fundus of the lateral sulcus to surface cortex near the anterior tip of the intraparietal sulcus. Two additional topographically organized maps are likely in Ri. These are “worm-like” body maps oriented along the A-P axis and joined at the head representation. Connections with the center of Ig are not somatotopically organized.
The diversity of somatosensory areas in lateral parietal cortex revealed by the labeled connections was discussed in reference to prior mapping of SII in monkeys and was compared to reports of multiple areas in this region of cortex in other species.
TL;DR: The gephyrin present at GABAergic synapses of the retina might also be involved with clustering of receptors at the postsynaptic sites and can no longer be considered as a unique marker of glycinergicsynapses.
Abstract: Gephyrin is a protein that copurifies with the glycine receptor (GlyR) and is required for the clustering of GlyRs at postsynaptic sites. Previously, it was thought that antibody mAb 7a, directed against gephyrin, was a specific marker for GlyR. However, there is evidence that gephyrin can also be found at nonglycinergic synapses. Here, immunocytochemistry was applied to show this directly for the rat retina. Both gephyrin and different Subunits of the γ-aminobutyric acid (GABA)A receptor were localized to discrete puncta in the inner plexiform layer, and these puncta were shown by electron microscopy to represent synaptic sites. Double immunocytochemistry revealed that GABAA receptors and GlyRs are not colocalized. However, gephyrin and different subunits of GABAA receptors were found to occur at the same synapses. The amount of colocalization varied with the GABAA receptor subunit composition and was most extensive for the α2 subunit, less for the α3 subunit, and minimal for the αl subunit. The gephyrin present at GABAergic synapses of the retina might also be involved with clustering of receptors at the postsynaptic sites. Hence, localization of gephyrin can no longer be considered as a unique marker of glycinergic synapses. © 1995 Wiley-Liss, Inc.
TL;DR: Focal injections of the anterograde tracer biocytin were made into physiologically identified loci of the CNIC and the spatial organisation of the labeled fibres was revealed with computer‐assisted threedimensional (3‐D) reconstruction.
Abstract: We present a comprehensive description of the local (intrinsic and commissural) connections in the central nucleus of the inferior colliculi (CNICs) in guinea pig. Focal injections of the anterograde tracer biocytin were made into physiologically identified loci of the CNIC and the spatial organisation of the labeled fibres was revealed with computer-assisted threedimensional (3-D) reconstruction.
The intrinsic fibres form a series of V-shaped laminar plexuses composed of fibres bearing both terminal and en passant boutons. Each laminar plexus has a central wing located in the CNIC that extends into the dorsal cortex and an external wing located in the external cortex. The edge where the two wings intersect delimits the lateral border of the central nucleus with the external cortex. The density of labeled terminals was consistently lower in the cortices than in the CNIC. The laminar plexus connects points of similar frequency within the CNIC. Seen in 3-D, the location, orientation, shape, and area of the laminar plexus vary as a function of best frequency. The commissural fibres ending in the contralateral IC to the injection also form a laminar plexus which is symmetrical to the ipsilateral plexus. Electrolytic lesions placed in the contralateral IC at sites with best frequencies corresponding to those of the injection coincided with the terminals of the commissural fibres in most instances. Possible patterns for the organisation of these connections (point-to-point and diverging) are discussed.
Three systems of peripheral axons to the laminar plexus are described: parallel, oblique, and perpendicular to the central wing. The novel parallel system has terminals in both ICs that run parallel to the central wing. It might constitute the anatomical basis for across-frequency interactions. The oblique and perpendicular systems are fibres of passage projecting to the commissure and brachium of the IC, respectively. © 1995 Wiley-Liss, Inc.
TL;DR: The results suggest that POU‐III transcription factors help define specific regions in the early neuroepithelium as well as different cellular phenotypes in the ventricular, subventricular, and mantle layers of specific regions later in development.
Abstract: In situ hybridization was used to map spatiotemporal expression patterns of the four known intronless POU-III transcription factor genes Brn-1, Brn-2, Brn-4, and Tst-1 in the developing rat forebrain vesicle, beginning on embryonic day 10. The results indicate that the proliferation layers (ventricular and subventricular) and mantle layer of the forebrain neural tube each display a strikingly unique pattern of regionalized POU-III expression. Within a particular region, or layer within a region, none to all four of the mRNAs may be detected, and during development a particular mRNA in a particular region displays one of five expression patterns, or a combination of these patterns, which may be described as conserved, lost, transient, acquired, or redeployed expression. In the developing brain as a whole, Brn-1 and Brn-2 early on display somewhat different spatial expression patterns that converge to essential identity in the adult, whereas Brn-4 expression is initially broad and becomes much more restricted in the adult, and Tst-1 expression expands greatly through development. Usually, though not always, expression patterns tend to correlate with major histological features in the forebrain (often internal or external sulci associated with proliferation zones), and little evidence for waves of expression moving through the whole forebrain over time was obtained. Thus, clear differences in hybridization intensity often are observed between the cerebral cortex, basal telencephalic nuclei, hypothalamus, ventral thalamus, dorsal thalamus, and pretectal region. In contrast, transverse bands of hybridization extending from the roof to the floor of the forebrain, corresponding to proposed neuromeres, were not observed with these probes. The results suggest that POU-III transcription factors help define specific regions in the early neuroepithelium as well as different cellular phenotypes in the ventricular, subventricular, and mantle layers of specific regions later in development. Thus, the functions of these regulatory proteins may be different in proliferating neuroepithelial cells, young neurons, and mature neurons and appear to be region-specific.