Cytoarchitecture and musculotopic organization of the facial motor nucleus in Cebus apella monkey

The architecture and musculotopic organization of the facial motor nucleus in the Cebus apella monkey (a New World primate) were investigated using histological techniques and a multiple labelling strategy, in which horseradish peroxidase-conjugated neuroanatomical tracers (CTB-HRP and WGA-HRP) and fluorescent tracers were injected into individual facial muscles. The facial motor nucleus was formed by multipolar motoneurons and had an ovoid shape, with its rostrocaudal axis measuring on average 1875 mum. We divided the nucleus into four different subnuclei: medial, intermediate, dorsal and lateral. Retrograde labelling patterns revealed that individual muscles were innervated by longitudinal functional columns of motoneurons. The columns of the orbicularis oculi, zygomaticus, orbicularis oris, auricularis superior, buccinator and platysma muscles were located in the dorsal, intermediate, lateral, medial, lateral and intermediate subnuclei, respectively. However, the motoneuron columns of the levator labii superioris alaeque nasi muscle and frontalis muscle could not be associated with a specific subnucleus. The present results confirm previous studies regarding the musculotopic organization of the facial motor nucleus. However, we observed some particularities in terms of the relative size of each column in C. apella, which might be related to the functional and behavioral importance of each muscle in the particular context of this primate.

A comparative study of cytoarchitecture and serotonergic afferents in the suprachiasmatic nucleus of primates (Cebus apella and Callithrix jacchus) and rats (Wistar and Long Evans strains)

The suprachiasmatic nucleus, an essential diencephalic component of the circadian timing system, plays a role in the generation and modulation of behavioral and neuroendocrine rhythms in mammals. Its cytoarchitecture, neurochemical and hodological characteristics have been investigated in various mammalian species, particularly in rodents. In most species, two subdivisions, based on these aspects and considered to reflect functional specialization within the nucleus, can be recognized. Many studies reveal a typical dense innervation by serotonergic fibers in this nucleus, mainly in the ventromedial area, overlapping the retinal afferents. However, a different pattern occurs in certain animals, which lead us to investigate the distribution of serotonergic afferents in the suprachiasmatic nucleus of the Capuchin monkey, Cebus apella, compared to the marmoset, Callithrix jacchus, and two Rattus norvegicus lines (Long Evans and Wistar), and to reported findings for other mammalian species. Our morphometric data show the volume and length of the suprachiasmatic nucleus along the rostrocaudal axis to be greatest in C. apella > C. jacchus > Long Evans ≥ Wistar rats, in agreement with their body sizes. In C. apella, however, the serotonergic terminals occupy only some 10% of the nucleus' area, less than the 25% seen in the marmoset and rats. The distribution of the serotonergic fibers in C. apella does not follow the characteristic ventral organization pattern seen in the rodents. These findings raise questions concerning the intrinsic organization of the nucleus, as well as regarding the functional relationship between serotonergic input and retinal afferents in this diurnal species. © 2007 Elsevier B.V. All rights reserved.

The structure of Pavlovian fear conditioning in the amygdala

Do different brains forming a specific memory allocate the same groups of neurons to encode it? One way to test this question is to map neurons encoding the same memory and quantitatively compare their locations across individual brains. In a previous study, we used this strategy to uncover a common topography of neurons in the dorsolateral amygdala (LAd) that expressed a learning-induced and plasticity-related kinase (p42/44 mitogen-activated protein kinase; pMAPK), following auditory Pavlovian fear conditioning. In this series of experiments, we extend our initial findings to ask to what extent this functional topography depends upon intrinsic neuronal structure. We first showed that the majority (87 %) of pMAPK expression in the lateral amygdala was restricted to principal-type neurons. Next, we verified a neuroanatomical reference point for amygdala alignment using in vivo magnetic resonance imaging and in vitro morphometrics. We then determined that the topography of neurons encoding auditory fear conditioning was not exclusively governed by principal neuron cytoarchitecture. These data suggest that functional patterning of neurons undergoing plasticity in the amygdala following Pavlovian fear conditioning is specific to memory formation itself. Further, the spatial allocation of activated neurons in the LAd was specific to cued (auditory), but not contextual, fear conditioning. Spatial analyses conducted at another coronal plane revealed another spatial map unique to fear conditioning, providing additional evidence that the functional topography of fear memory storing cells in the LAd is non-random and stable. Overall, these data provide evidence for a spatial organizing principle governing the functional allocation of fear memory in the amygdala.

Anatomical specializations for enhanced olfactory sensitivity in kiwi, Apteryx mantelli

The ability to function in a nocturnal and ground-dwelling niche requires a unique set of sensory specializations. The New Zealand kiwi has shifted away from vision, instead relying on auditory and tactile stimuli to function in its environment and locate prey. Behavioral evidence suggests that kiwi also rely on their sense of smell, using olfactory cues in foraging and possibly also in communication and social interactions. Anatomical studies appear to support these observations: the olfactory bulbs and tubercles have been suggested to be large in the kiwi relative to other birds, although the extent of this enlargement is poorly understood. In this study, we examine the size of the olfactory bulbs in kiwi and compare them with 55 other bird species, including emus, ostriches, rheas, tinamous, and 2 extinct species of moa (Dinornithiformes). We also examine the cytoarchitecture of the olfactory bulbs and olfactory epithelium to determine if any neural specializations beyond size are present that would increase olfactory acuity. Kiwi were a clear outlier in our analysis, with olfactory bulbs that are proportionately larger than those of any other bird in this study. Emus, close relatives of the kiwi, also had a relative enlargement of the olfactory bulbs, possibly supporting a phylogenetic link to well-developed olfaction. The olfactory bulbs in kiwi are almost in direct contact with the olfactory epithelium, which is indeed well developed and complex, with olfactory receptor cells occupying a large percentage of the epithelium. The anatomy of the kiwi olfactory system supports an enhancement for olfactory sensitivities, which is undoubtedly associated with their unique nocturnal niche.

The subcortical confinement hypothesis: A neurological model for schizotypal hallucinations

Introduction Different types of hallucinations are symptomatic of different conditions. Schizotypal hallucinations are unique in that they follow existing delusional narrative patterns: they are often bizarre, they are generally multimodal, and they are particularly vivid (the experience of a newsreader abusing you personally over the TV is both visual and aural. Patients who feel and hear silicone chips under their skin suffer from haptic hallucinations as well as aural ones, etc.) Although there are a number of hypotheses for hallucinations, few cogently grapple the sheer bizarreness of the ones experienced in schizotypal psychosis. Methods A review-based hypothesis, traversing theory from the molecular level to phenomenological expression as a distinct and recognizable symptomatology. Conclusion Hallucinations appear to be caused by a two-fold dysfunction in the mesofrontal dopamine pathway, which is considered here to mediate attention of different types: in the anterior medial frontal lobe, the receptors (largely D1 type) mediate declarative awareness, whereas the receptors in the striatum (largely D2 type) mediate latent awareness of known schemata. In healthy perception, most of the perceptual load is performed by the latter: by the top-down predictive and mimetic engine, with the bottom-up mechanism being used as a secondary tool to bring conscious deliberation to stimuli that fails to match up against expectations. In schizophrenia, the predictive mode is over-stimulated, while the bottom-up feedback mechanism atrophies. The dysfunctional distribution pattern effectively confines dopamine activity to the striatum, thereby stimulating the structural components of thought and behaviour: well-learned routines, narrative structures, lexica, grammar, schemata, archetypes, and other procedural resources. Meanwhile, the loss of activity in the frontal complex reduces the capacity for declarative awareness and for processing anything that fails to meet expectations.

High-resolution SNP microarray investigation of copy number variations on chromosome 18 in a control cohort

Copy number variations (CNVs) as described in the healthy population are purported to contribute significantly to genetic heterogeneity. Recent studies have described CNVs using lymphoblastoid cell lines or by application of specifically developed algorithms to interrogate previously described data. However, the full extent of CNVs remains unclear. Using high-density SNP array, we have undertaken a comprehensive investigation of chromosome 18 for CNV discovery and characterisation of distribution and association with chromosome architecture. We identified 399 CNVs, of which loss represents 98%, 58% are less than 2.5 kb in size and 71% are intergenic. Intronic deletions account for the majority of copy number changes with gene involvement. Furthermore, one-third of CNVs do not have putative breakpoints within repetitive sequences. We conclude that replicative processes, mediated either by repetitive elements or microhomology, account for the majority of CNVs in the healthy population. Genomic instability involving the formation of a non-B structure is demonstrated in one region.

Avaliação morfofuncional do complexo hipocampal em ratos submetidos a um modelo de hipóxia-isquemia pré-natal

A diminuição do aporte de oxigênio e nutrientes na vida perinatal resulta em danos, como astrogliose, morte de neurônios e de células proliferativas. Déficits cognitivos podem estar relacionados a danos no hipocampo. Neste trabalho avaliamos a citoarquitetura do giro dentado (DG) durante o desenvolvimento e a memória de ratos submetidos à HI. Para tal, utilizamos a técnica de imunohistoquímica para marcador de proliferação celular (KI67), neurônio jovem (DCX), de astrócitos (GFAP) e de óxido nítrico sintase neuronal (NOSn). Para avaliar a memória de curta e de longa duração foi utilizado o teste de reconhecimento de objetos (RO). Ratas Wistar grávidas em E18 foram anestesiadas (tribromoetanol) e as quatro artérias uterinas foram ocluídas com grampos de aneurisma (Grupo HI). Após 45 minutos, os grampos foram removidos e foi feita a sutura por planos anatômicos. Os animais do grupo controle (SHAM) sofreram o mesmo procedimento, excetuando a oclusão das artérias. Os animais nasceram a termo. Animais com idades de 7 a 90 dias pós-natal (P7 a P90), foram anestesiados e perfundido-fixados com paraformaldeído a 4%, e os encéfalos submetidos ao processamento histológico. Cortes coronais do hipocampo (20m) foram submetidos à imunohistoquímica para KI67, DCX, GFAP e NOSn. Animais P90 foram submetidos ao RO. Os procedimentos foram aprovados pelo comitê de ética (CEA/019/2010). Observamos menor imunomarcação para KI67 no giro dentado de animais HI em P7. Para a marcação de DCX nesta idade não foi observada diferença entre os grupos. Animais HI em P15, P20 e P45 tiveram menor imunomarcação para DCX e Ki67 na camada granular. Animais P90 de ambos os grupos não apresentaram marcação para KI67 e DCX. Vimos aumento da imunomarcação para GFAP nos animais HI em todas as idades. A imunomarcação para NOSn nos animais HI foi menor em todas as idades. O maior número de células NOSn positivas foi visto em animais P7 em ambos os grupos na camada polimórfica. Em P15, animais HI apresentam células NOSn+ em todo o DG. Em P30 animais HI apresentam células NOSn+ nas camadas polimórfica e sub-granular. Animais adultos (P90) de ambos os grupos apresentam células NOSn positivas apenas nas camadas granular e sub-granular. Embora animais HI P90 não apresentaram déficits de memória, estes apresentaram menor tempo de exploração do objeto. Comportamento correspondente a déficits de atenção em humanos. Nossos resultados sugerem que HI perinatal diminui a população de células proliferativas, de neurônios jovens, de neurônios NOSn+, além de causar astrogliose e possivelmente déficits de atenção. O modelo demonstrou ser útil para a compreensão dos mecanismos celulares das lesões hipóxico-isquêmicas e pode ser usado para testar estratégias terapêuticas.

The cytolytic molecules Fas ligand and TRAIL are required for murine thymic graft-versus-host disease.

Thymic graft-versus-host disease (tGVHD) can contribute to profound T cell deficiency and repertoire restriction after allogeneic BM transplantation (allo-BMT). However, the cellular mechanisms of tGVHD and interactions between donor alloreactive T cells and thymic tissues remain poorly defined. Using clinically relevant murine allo-BMT models, we show here that even minimal numbers of donor alloreactive T cells, which caused mild nonlethal systemic graft-versus-host disease, were sufficient to damage the thymus, delay T lineage reconstitution, and compromise donor peripheral T cell function. Furthermore, to mediate tGVHD, donor alloreactive T cells required trafficking molecules, including CCR9, L selectin, P selectin glycoprotein ligand-1, the integrin subunits alphaE and beta7, CCR2, and CXCR3, and costimulatory/inhibitory molecules, including Ox40 and carcinoembryonic antigen-associated cell adhesion molecule 1. We found that radiation in BMT conditioning regimens upregulated expression of the death receptors Fas and death receptor 5 (DR5) on thymic stromal cells (especially epithelium), while decreasing expression of the antiapoptotic regulator cellular caspase-8-like inhibitory protein. Donor alloreactive T cells used the cognate proteins FasL and TNF-related apoptosis-inducing ligand (TRAIL) (but not TNF or perforin) to mediate tGVHD, thereby damaging thymic stromal cells, cytoarchitecture, and function. Strategies that interfere with Fas/FasL and TRAIL/DR5 interactions may therefore represent a means to attenuate tGVHD and improve T cell reconstitution in allo-BMT recipients.

Architectonic subdivisions of the amygdalar complex of a primitive marsupial (Didelphis aurita)

The architecture of the amygdaloid complex of a marsupial, the opossum Didelphis aurita, was analyzed using classical stains like Nissl staining and myelin (Gallyas) staining, and enzyme histochemistry for acetylcholinesterase and NADPH-diaphorase. Most of the subdivisions of the amygdaloid complex described in eutherian mammals were identified in the opossum brain. NADPH-diaphorase revealed reactivity in the neuropil of nearly all amygdaloid subdivisions with different intensities, allowing the identification of the medial and lateral subdivisions of the cortical posterior nucleus and the lateral subdivision of the lateral nucleus. The lateral, central, basolateral and basomedial nuclei exhibited acetylcholinesterase positivity, which provided a useful chemoarchitectural criterion for the identification of the anterior basolateral nucleus. Myelin stain allowed the identification of the medial subdivision of the lateral nucleus, and resulted in intense staining of the medial subdivisions of the central nucleus. The medial, posterior, and cortical nuclei, as well as the amygdalopiriform area did not exhibit positivity for myelin staining. On the basis of cyto- and chemoarchitectural criteria, the present study highlights that the opossum amygdaloid complex shares similarities with that of other species, thus supporting the idea that the organization of the amygdala is part of a basic plan conserved through mammalian evolution. (C) 2008 Elsevier Inc. All rights reserved.

Effects of long-term diabetes on the structure and cell proliferation of the myometrium in the early pregnancy of mice

P>It is known that the development of diabetic complications in human pregnancy is directly related to the severity and the duration of this pathology. In this study, we developed a model of long-term type 1 diabetes to investigate its effects on the cytoarchitecture, extracellular matrix and cell proliferation during the first adaptation phase of the myometrium for pregnancy. A single dose of alloxan was used to induce diabetes in mice prior to pregnancy. To identify the temporal effects of diabetes the mice were divided into two groups: Group D1 (females that became pregnant 90-100 days after alloxan); Group D2 (females that became pregnant 100-110 days after alloxan). Uterine samples were collected after 168 h of pregnancy and processed for light and electron microscopy. In both groups the histomorphometric evaluation showed that diabetes promoted narrowing of the myometrial muscle layers which was correlated with decreased cell proliferation demonstrated by PCNA immunodetection. In D1, diabetes increased the distance between muscle layers and promoted oedema. Contrarily, in D2 the distance between muscle layers decreased and, instead of oedema, there was a markedly deposition of collagen in the myometrium. Ultrastructural analysis showed that diabetes affects the organization of the smooth muscle cells and their myofilaments. Consistently, the immunoreaction for smooth muscle alpha-actin revealed clear disorganization of the contractile apparatus in both diabetic groups. In conclusion, the present model demonstrated that long-term diabetes promotes significant alterations in the myometrium in a time-sensitive manner. Together, these alterations indicate that diabetes impairs the first phenotypic adaptation phase of the pregnant myometrium.

Astrócitos imunorreativos à proteína glial fibrilar ácida (GFAP) em sistema nervoso central de equinos normais e de equinos com leucoencefalomalácia

A proteína glial fibrilar ácida (GFAP), subunidade dos filamentos intermediários do citoesqueleto celular, está presente no citoplasma de astrócitos. Técnicas imunohistoquímicas com anticorpos primários anti-GFAP são geralmente empregadas para identificar astrócitos no sistema nervoso, permitindo verificar também sua hipertrofia. Vários estudos mostram a distribuição, a morfologia e a citoarquitetura de astrócitos em várias regiões do SNC do homem e de animais de laboratório. No entanto, em animais domésticos e, especialmente em equinos, poucas informações estão disponíveis. No presente trabalho, verificou-se a densidade e a morfologia de astrócitos imunorreativos à GFAP na substância branca da córtex cerebral de equinos com leucoencefalomalácia (LEM) comparando-se esses aspectos com o de equinos normais. Animais com LEM apresentaram hipertrofia de astrócitos em áreas próximas às lesões, representada pelo aumento do corpo celular, do núcleo e dos prolongamentos citoplasmáticos. O número de astrócitos apresentou-se reduzido e a imunorreatividade foi mais acentuada. Nos animais normais, verificou-se distribuição constante de astrócitos imunorreagentes com características de fibrosos. Alterações vasculares nos animais com LEM, como por exemplo degeneração de endotélio vascular, também foram observadas, podendo estar associadas às alterações astrocíticas.

O complexo nuclear vestibular do sagui (callithrix jacchus): caracterização citoarquitetônica e neuroquímica

To the vertebrates, maintain body balance against the gravitational field and be able to orient themselves in the environment are fundamental aspects for survival, in which the participation of vestibular system is essential. As part of this system, the vestibular nuclear complex is the first central station that, by integrating many information (visual, proprioceptive), and the vestibular, assumes the lead role in maintaining balance. In this study, the vestibular nuclear complex was evaluated in relation to its cytoarchitecture and neurochemical content of cells and axon terminals, through the techniques of Nissl staining and immunohistochemistry for neuronal specific nuclear protein (NeuN), glutamate (Glu), substance P (SP), choline acetyltransferase (ChAT) (enzyme that synthesizes acetylcholine-Ach) and glutamic acid decarboxylase (GAD) (enzyme that synthesizes gamma-amino butyric acid-GABA). The common marmoset (Callithrix jacchus) was used as experimental animal, which is a small primate native from the Atlantic Forest in the Brazilian Northeast. As results, the Nissl technique, complemented by immunohistochemistry for NeuN allowed to delineate the vestibular nucleus superior, lateral, medial and inferior (or descending) in the brain of the common marmoset. Neurons and terminals immunoreactive to Glu and ChAT and only immunoreactive terminals to SP and GAD were seen in all nuclei, although in varying density. This study confirms the presence in the vestibular nuclei of the common marmoset, of Glu and SP in terminals, probably from the first order neurons of vestibular ganglion, and of GABA in terminals, presumably from Purkinge cells of the cerebellum. Second-order neurons of the vestibular nuclei seem to use Glu and Ach as neurotransmitters, judging by their expressive presence in the cell bodies of these nuclei in common marmosets, as reported in other species

Evolutionary Changes in the Complexity of the Tectum of Nontetrapods: A Cladistic Approach

Background: The tectum is a structure localized in the roof of the midbrain in vertebrates, and is taken to be highly conserved in evolution. The present article assessed three hypotheses concerning the evolution of lamination and citoarchitecture of the tectum of nontetrapod animals: 1) There is a significant degree of phylogenetic inertia in both traits studied (number of cellular layers and number of cell classes in tectum); 2) Both traits are positively correlated accross evolution after correction for phylogeny; and 3) Different developmental pathways should generate different patterns of lamination and cytoarchitecture.Methodology/Principal Findings: The hypotheses were tested using analytical-computational tools for phylogenetic hypothesis testing. Both traits presented a considerably large phylogenetic signal and were positively associated. However, no difference was found between two clades classified as per the general developmental pathways of their brains.Conclusions/Significance: The evidence amassed points to more variation in the tectum than would be expected by phylogeny in three species from the taxa analysed; this variation is not better explained by differences in the main course of development, as would be predicted by the developmental clade hypothesis. Those findings shed new light on the evolution of an functionally important structure in nontetrapods, the most basal radiations of vertebrates.

"O núcleo supraquiasmático e o folheto intergeniculado do mocó (Kerodon rupestris): Projeções retinianas e caracterização imuno-histoquímica

In this study, two circadian related centres, the suprachiasmatic nucleus (SCN) and the intergeniculate leaflet (IGL) were evaluated in respect to their cytoarchitecture, retinal afferents and chemical content of major cells and axon terminals with a tract tracer and immunohistochemical techniques in the rock cavy (Kerodon rupestris), a Brazilian caviidae rodent species. The rock cavy SCN is innervated in its ventral portion by terminals from the predominantly contralateral retina. It also contains neurophisin and vasoactive intestinal polypeptide immunoreactive cell bodies and neuropeptide Y and enkephalin immunopositive fibres and terminals and is marked by intense GFAP immunoreactivity. The IGL receives a predominantly contralateral retinal projection, contains neuropeptide Y and nitric oxide synthase producing neurons and enkephalin immunopositive terminals and is characterized by dense GFAP immunoreactivity. This is the first report examining the neural circadian system in a crepuscular rodent species for which circadian properties have been described. The results are discussed comparing with what has been described for other species and in the context of the functional significance of these centres