RESUMEN

Melanin-concentrating hormone (MCH) is a ubiquitous vertebrate neuropeptide predominantly synthesized by neurons of the diencephalon that can act through two G protein-coupled receptors, called MCHR1 and MCHR2. The expression of Mchr1 has been investigated in both rats and mice, but its synthesis remains poorly described. After identifying an antibody that detects MCHR1 with high specificity, we employed immunohistochemistry to map the distribution of MCHR1 in the CNS of rats and mice. Multiple neurochemical markers were also employed to characterize some of the neuronal populations that synthesize MCHR1. Our results show that MCHR1 is abundantly found in a subcellular structure called the primary cilium, which has been associated, among other functions, with the detection of free neurochemical messengers present in the extracellular space. Ciliary MCHR1 was found in a wide range of areas, including the olfactory bulb, cortical mantle, striatum, hippocampal formation, amygdala, midline thalamic nuclei, periventricular hypothalamic nuclei, midbrain areas, and in the spinal cord. No differences were observed between male and female mice, and interspecies differences were found in the caudate-putamen nucleus and the subgranular zone. Ciliary MCHR1 was found in close association with several neurochemical markers, including tyrosine hydroxylase, calretinin, kisspeptin, estrogen receptor, oxytocin, vasopressin, and corticotropin-releasing factor. Given the role of neuronal primary cilia in sensing free neurochemical messengers in the extracellular fluid, the widespread distribution of ciliary MCHR1, and the diverse neurochemical populations who synthesize MCHR1, our data indicate that nonsynaptic communication plays a prominent role in the normal function of the MCH system.

Asunto(s)

Encéfalo/metabolismo , Cilios/metabolismo , Receptores de Somatostatina/biosíntesis , Caracteres Sexuales , Animales , Cilios/genética , Femenino , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Ratas , Ratas Long-Evans , Ratas Sprague-Dawley , Receptores de Somatostatina/genética

RESUMEN

The early patterning of the thalamus during embryonic development defines rostral and caudal progenitor domains, which are conserved from fishes to mammals. However, the subsequent developmental mechanisms that lead to the adult thalamic configuration have only been investigated for mammals and other amniotes. In this study, we have analyzed in the anuran amphibian Xenopus laevis (an anamniote vertebrate), through larval and postmetamorphic development, the progressive regional expression of specific markers for the rostral (GABA, GAD67, Lhx1, and Nkx2.2) and caudal (Gbx2, VGlut2, Lhx2, Lhx9, and Sox2) domains. In addition, the regional distributions at different developmental stages of other markers such as calcium binding proteins and neuropeptides, helped the identification of thalamic nuclei. It was observed that the two embryonic domains were progressively specified and compartmentalized during premetamorphosis, and cell subpopulations characterized by particular gene expression combinations were located in periventricular, intermediate and superficial strata. During prometamorphosis, three dorsoventral tiers formed from the caudal domain and most pronuclei were defined, which were modified into the definitive nuclear configuration through the metamorphic climax. Mixed cell populations originated from the rostral and caudal domains constitute most of the final nuclei and allowed us to propose additional subdivisions in the adult thalamus, whose main afferent and efferent connections were assessed by tracing techniques under in vitro conditions. This study corroborates shared features of early gene expression patterns in the thalamus between Xenopus and mouse, however, the dynamic changes in gene expression observed at later stages in the amphibian support mechanisms different from those of mammals.

Asunto(s)

Tipificación del Cuerpo/fisiología , Neurogénesis/fisiología , Neuronas/citología , Núcleos Talámicos/embriología , Animales , Desarrollo Embrionario , Proteína Homeobox Nkx-2.2 , Xenopus laevis

RESUMEN

Glucagon-like peptide-1 (GLP-1) is an incretin hormone with a number of functions to maintain energy homeostasis and contribute to motivated behavior, both peripherally and within the central nervous system (CNS). These functions, which include insulin secretion, gastric emptying, satiety, and the hedonic aspects of food and drug intake, are primarily mediated through stimulation of the GLP-1 receptor. While this receptor plays an important role in a variety of physiological outcomes, data regarding its CNS expression has been primarily limited to regional receptor binding and single-label transcript expression studies. We thus developed a bacterial artificial chromosome transgenic mouse, in which expression of a red fluorescent protein (mApple) is driven by the GLP-1R promoter. Using this reporter mouse, we characterized the regional and cellular expression patterns of GLP-1R expressing cells in the CNS, using double-label immunohistochemistry and in situ hybridization. GLP-1R-expressing cells were enriched in several key brain regions and circuits, including the lateral septum, hypothalamus, amygdala, bed nucleus of the stria terminalis, hippocampus, ventral midbrain, periaqueductal gray, and cerebral cortex. In most regions, GLP-1R primarily colocalized with GABAergic neurons, except within some regions such as the hippocampus, where it was co-expressed in glutamatergic neurons. GLP-1R-mApple cells were highly co-expressed with 5-HT3 receptor-containing neurons within the cortex and striatum, as well as with dopamine receptor- and calbindin-expressing cells within the lateral septum, the brain region in which GLP-1R is most highly expressed. In this manuscript, we provide detailed images of GLP-1R-mApple expression and distribution within the brain and characterization of these neurons.

Asunto(s)

Encéfalo/metabolismo , Péptido 1 Similar al Glucagón/metabolismo , Neuronas/metabolismo , Animales , Ratones , Ratones Transgénicos , Modelos Animales , Transcriptoma

RESUMEN

Considerable evidence supports the premise that the visual system of primates develops hierarchically, with primary visual cortex developing structurally and functionally first, thereby influencing the subsequent development of higher cortical areas. An apparent exception is the higher order middle temporal visual area (MT), which appears to be histologically distinct near the time of birth in marmosets. Here we used a number of histological and immunohistological markers to evaluate the maturation of cortical and subcortical components of the visual system in galagos ranging from newborns to adults. Galagos are representative of the large strepsirrhine branch of primate evolution, and studies of these primates help identify brain features that are broadly similar across primate taxa. The histological results support the view that MT is functional at or near the time of birth, as is primary visual cortex. Likewise, the superior colliculus, dorsal lateral geniculate nucleus, and the posterior nucleus of the pulvinar are well-developed by birth. Thus, these subcortical structures likely provide visual information directly or indirectly to cortex in newborn galagos. We conclude that MT resembles a primary sensory area by developing early, and that the early development of MT may influence the subsequent development of dorsal stream visual areas.

Asunto(s)

Galagidae/crecimiento & desarrollo , Pulvinar/crecimiento & desarrollo , Colículos Superiores/crecimiento & desarrollo , Corteza Visual/crecimiento & desarrollo , Factores de Edad , Animales , Cuerpos Geniculados/citología , Cuerpos Geniculados/crecimiento & desarrollo , Pulvinar/citología , Colículos Superiores/citología , Corteza Visual/citología , Vías Visuales/citología , Vías Visuales/crecimiento & desarrollo

RESUMEN

The Pax6 gene encodes a regulatory transcription factor that is key in brain development. The molecular structure of Pax6, the roles it plays and its patterns of expression in the brain have been highly conserved during vertebrate evolution. As neurodevelopment proceeds, the Pax6 expression changes from the mitotic germinal zone in the ventricular zone to become distributed in cell groups in the adult brain. Studies in various vertebrates, from fish to mammals, found that the Pax6 expression is maintained in adults in most regions that express it during development. Specifically, in amphibians, Pax6 is widely expressed in the adult brain and its distribution pattern serves to highlight regional organization of the brain. In the present study, we analyzed the detailed distribution of Pax6 cells in the adult central nervous system of lungfishes, the closest living relatives of all tetrapods. Immunohistochemistry performed using double labeling techniques with several neuronal markers of known distribution patterns served to evaluate the actual location of Pax6 cells. Our results show that the Pax6 expression is maintained in the adult brain of lungfishes, in distinct regions of the telencephalon (pallium and subpallium), diencephalon, mesencephalon, hindbrain, spinal cord, and retina. The pattern of Pax6 expression is largely shared with amphibians and helps to understand the primitive condition that would have characterized the common ancestors to all sarcopterygians (lobe-finned fishes and tetrapods), in which Pax6 would be needed to maintain specific entities of subpopulations of neurons.

Asunto(s)

Química Encefálica , Encéfalo/anatomía & histología , Encéfalo/metabolismo , Factor de Transcripción PAX6/biosíntesis , Animales , Química Encefálica/fisiología , Peces , Expresión Génica , Factor de Transcripción PAX6/análisis , Factor de Transcripción PAX6/genética , Vertebrados

RESUMEN

Traumatic brain injury (TBI) can result in excitation: inhibition imbalance, as well as a range of chronic neurological deficits. However, how TBI affects different interneurons, and how this relates to behavioral abnormalities, remains poorly understood. This study examined the effects of a mixed diffuse-focal model of TBI, the lateral fluid percussion injury (LFPI), on interneurons, 8 weeks post-TBI in rats. Brains were labeled with antibodies against calbindin, parvalbumin, calretinin, neuropeptide Y, and somatostatin, and the number of interneurons were assessed in the cortex and hippocampus following LFPI. LFPI caused a reduction in the numbers of interneurons mediating both perisomatic and dendritic inhibition in the somatosensory cortex. In hippocampus, there were heterogenous changes in the number of interneurons while motor cortex, showed no obvious loss in any of the subsets of interneurons after TBI. In parallel to the investigations of changes in the number of interneurons, we also investigated the long-term behavioral consequences of LFPI. Behaviorally, rats given an LFPI displayed transient reduction in performance in motor tasks and were significantly impaired in reversal learning in the water maze task post-TBI. We also report here progressive neurodegeneration in cortex and hippocampus indicated by Fluoro-Jade C in the different brain areas examined after injury. Our findings suggest differential vulnerability of inhibitory neurons to LFPI in the different brain areas examined after injury. These data will aid in evaluation of new treatments for TBI and help target specific neuronal subtypes as a function of injury time and type.

Asunto(s)

Lesiones Traumáticas del Encéfalo/patología , Encéfalo/patología , Interneuronas/patología , Animales , Encéfalo/fisiopatología , Lesiones Traumáticas del Encéfalo/fisiopatología , Modelos Animales de Enfermedad , Masculino , Degeneración Nerviosa/patología , Degeneración Nerviosa/fisiopatología , Ratas , Ratas Sprague-Dawley

RESUMEN

The primate visual brain possesses a myriad of pathways, whereby visual information originating at the retina is transmitted to multiple subcortical areas in parallel, before being relayed onto the visual cortex. The dominant retinogeniculostriate pathway has been an area of extensive study, and Vivien Casagrande's work in examining the once overlooked koniocellular pathway of the lateral geniculate nucleus has generated interest in how alternate subcortical pathways can contribute to visual perception. Another subcortical visual relay center is the inferior pulvinar (PI), which has four subdivisions and numerous connections with other subcortical and cortical areas and is directly recipient of retinal afferents. The complexity of subcortical connections associated with the PI subdivisions has led to differing results from various groups. A particular challenge in determining the exact connectivity pattern has been in accurately targeting the subdivisions of the PI with neural tracers. Therefore, in the present study, we used a magnetic resonance imaging (MRI)-guided stereotaxic injection system to inject bidirectional tracers in the separate subdivisions of the PI, the superior layers of the superior colliculus, the retina, and the lateral geniculate nucleus. Our results have determined for the first time that the medial inferior pulvinar (PIm) is innervated by widefield retinal ganglion cells (RGCs), and this pathway is not a collateral branch of the geniculate and collicular projecting RGCs. Furthermore, our tracing data shows no evidence of collicular terminations in the PIm, which are confined to the centromedial and posterior PI.

Asunto(s)

Red Nerviosa/fisiología , Pulvinar/fisiología , Retina/fisiología , Vías Visuales/fisiología , Animales , Callithrix , Femenino , Cuerpos Geniculados/citología , Cuerpos Geniculados/fisiología , Masculino , Red Nerviosa/citología , Primates , Pulvinar/citología , Células Ganglionares de la Retina/fisiología , Colículos Superiores/citología , Colículos Superiores/fisiología , Vías Visuales/citología

RESUMEN

In primate retina, the midget, parasol, and small bistratified cell populations form the large majority of ganglion cells. In addition, there is a variety of low-density wide-field ganglion cell types that are less well characterized. Here we studied retinal ganglion cells in the common marmoset, Callithrix jacchus, using particle-mediated gene transfer. Ganglion cells were transfected with an expression plasmid for the postsynaptic density 95-green fluorescent protein. The retinas were processed with established immunohistochemical markers for bipolar and/or amacrine cells to determine ganglion cell dendritic stratification. In total over 500 ganglion cells were classified based on their dendritic field size, morphology, and stratification in the inner plexiform layer. Over 17 types were distinguished, including midget, parasol, broad thorny, small bistratified, large bistratified, recursive bistratified, recursive monostratified, narrow thorny, smooth monostratified, large sparse, giant sparse (melanopsin) ganglion cells, and a group that may contain several as yet uncharacterized types. Assuming each characterized type forms a hexagonal mosaic, the midget and parasol cells account for over 80% of all ganglion cells in the central retina but only ∼50% of cells in the peripheral (>2 mm) retina. We conclude that the fovea is dominated by midget and parasol cells, but outside the fovea the ganglion cell diversity in marmoset is likely as great as that reported for nonprimate retinas. Taken together, the ganglion cell types in marmoset retina resemble those described previously in macaque retina with respect to morphology, stratification, and change in proportion across the retina.

Asunto(s)

Callithrix/anatomía & histología , Células Ganglionares de la Retina/clasificación , Células Ganglionares de la Retina/citología , Animales , Femenino , Masculino

RESUMEN

Neuregulin-3 (Nrg3) is a member of the Nrg family of growth factors identified as risk factors for schizophrenia. There are three Nrgs expressed in the nervous system (Nrg1-3) and of these Nrg1 has been the best characterized. To set the groundwork for elucidating neural roles for Nrg3, we studied its expression in the rat brain at both the RNA and protein levels. Using an antibody developed against Nrg3, we observed a developmental increase of Nrg3 protein expression from embryonic stages to adulthood and determined that it carries O-linked carbohydrates. In cortical neuronal cultures, transfected Neuro2a cells, and brain tissue sections Nrg3 protein was localized to the soma, neurites, and to the Golgi apparatus, where it is prominently expressed. Nrg3 was detected in excitatory, GABAergic and parvalbumin-expressing inhibitory neurons while expression in glia was limited. Nrg3 mRNA and protein were widely expressed during both embryonic and postnatal ages. At E17, Nrg3 was detected within the cortical plate and ventricular zone suggesting possible roles in cell proliferation or migration. At postnatal ages, Nrg3 was abundantly expressed throughout the cerebral cortex and hippocampus. Multiple thalamic nuclei expressed Nrg3, while detection in the striatum was limited. In the cerebellum, Nrg3 was found in both Purkinje cells and granule neurons. In the rodent brain, Nrg3 is the most abundantly expressed of the Nrgs and its patterns of expression differ both temporally and spatially from that of Nrg1 and Nrg2. These findings suggest that Nrg3 plays roles that are distinct from the other Nrg family members.

Asunto(s)

Encéfalo/metabolismo , Neurregulinas/metabolismo , Neurogénesis/fisiología , Neuronas/metabolismo , Animales , Ratas , Ratas Sprague-Dawley

RESUMEN

Recent evidence demonstrates that the pulvinar nuclei play a critical role in shaping the connectivity and function of the multiple cortical areas they connect. Surprisingly, however, little is known about the development of this area, the largest corpus of the thalamic nuclei, which go on to occupy 40% of the adult thalamus in the human. It was proposed that the nonhuman primate and the human pulvinar develop according to very different processes, with a greatly reduced neurogenic period in nonhuman primate compared to human and divergent origins. In the marmoset monkey, we demonstrate that neurons populating the pulvinar are generated throughout gestation, suggesting that this aspect of development is more similar to the human than first predicted. While we were able to confirm the diencephalic source of pulvinar neurons, we provide new evidence contesting the presence of an additional niche in the telencephalon. Finally, our study defines new molecular markers that will simplify future investigations in the development and evolution of the pulvinar.

Asunto(s)

Callithrix/fisiología , Pulvinar/crecimiento & desarrollo , Acetilcolinesterasa/metabolismo , Animales , Animales Recién Nacidos , Proliferación Celular , Diencéfalo/embriología , Diencéfalo/crecimiento & desarrollo , Femenino , Regulación de la Expresión Génica , Inmunohistoquímica , Neurogénesis/fisiología , Neuronas/fisiología , Embarazo , Pulvinar/citología , Pulvinar/embriología , Tercer Ventrículo/citología , Tercer Ventrículo/embriología , Vías Visuales/fisiología

RESUMEN

INTRODUCTION: Release of the neuromodulator acetylcholine into cortical circuits supports cognition, although its precise role and mechanisms of action are not well understood. Little is known about functional differences in cholinergic modulatory effects across cortical model systems, but anatomical evidence suggests that such differences likely exist because, for example, the expression of cholinergic receptors differs profoundly both within and between species. METHODS: In the primary visual cortex (V1) of macaque monkeys, cholinergic receptors are strongly expressed by inhibitory interneurons. Using dual-immunofluorescence confocal microscopy, we examine m1 muscarinic acetylcholine receptor expression by two subclasses of inhibitory interneurons-identified by their expression of the calcium-binding proteins calbindin and calretinin-in the middle temporal extrastriate area (MT) of the macaque. RESULTS AND CONCLUSIONS: We find that the majority of calbindin-immunoreactive neurons (55%) and only few calretinin-immunoreactive neurons (10%) express the m1 acetylcholine receptor. These results differ from the pattern observed in V1 of the same species, lending further support to the notion that cholinergic modulation in the cortex is tuned such that different cortical compartments will respond to acetylcholine release in different ways.

Asunto(s)

Calbindina 2/metabolismo , Calbindinas/metabolismo , Receptores Muscarínicos/metabolismo , Corteza Visual/metabolismo , Animales , Macaca mulatta , Masculino , Microscopía Fluorescente , Modelos Animales , Neuronas/metabolismo

RESUMEN

The actual organization of the central nucleus of the amygdala (CEA) in the rat is mostly based on cytoarchitecture and the distribution of several cell types, as described by McDonald in 1982. Four divisions were identified by this author. However, since this original work, one of these divisions, the intermediate part, has not been consistently recognized based on Nissl-stained material. In the present study, we observed that a compact condensation of retrogradely labeled cells is found in the CEA after fluorogold injection in the anterior region of the tuberal lateral hypothalamic area (LHA) in the rat. We then searched for neurochemical markers of this cell condensation and found that it is quite specifically labeled for calbindin (Cb), but also contains calretinin (Cr), tyrosine hydroxylase (TH) and methionine-enkephalin (Met-Enk) immunohistochemical signals. These neurochemical features are specific to this cell group which, therefore, is distinct from the other parts of the CEA. We then performed cholera toxin injections in the mouse LHA to identify this cell group in this species. We found that neurons exist in the medial and rostral CEAl that project into the LHA but they have a less tight organization than in the rat.

Asunto(s)

Núcleo Amigdalino Central/fisiología , Animales , Calbindina 2/metabolismo , Calbindinas/metabolismo , Núcleo Amigdalino Central/anatomía & histología , Encefalina Metionina/metabolismo , Área Hipotalámica Lateral/anatomía & histología , Área Hipotalámica Lateral/fisiología , Inmunohistoquímica , Masculino , Ratones , Vías Nerviosas/anatomía & histología , Vías Nerviosas/metabolismo , Vías Nerviosas/fisiología , Neuronas/fisiología , Ratas , Ratas Sprague-Dawley , Tirosina 3-Monooxigenasa/metabolismo

RESUMEN

Titi monkeys are arboreal, diurnal New World monkeys whose ancestors were the first surviving branch of the New World radiation. In the current study, we use cytoarchitectonic and immunohistochemical characteristics to compare titi monkey subcortical structures associated with visual processing with those of other well-studied primates. Our goal was to appreciate features that are similar across all New World monkeys, and primates in general, versus those features that are unique to titi monkeys and other primate taxa. We examined tissue stained for Nissl substance, cytochrome oxidase (CO), acetylcholinesterase (AChE), calbindin (Cb), parvalbumin (Pv), and vesicular glutamate transporter 2 (VGLUT2) to characterize the superior colliculus, lateral geniculate nucleus, and visual pulvinar. This is the first study to characterize VGLUT2 in multiple subcortical structures of any New World monkey. Our results from tissue processed for VGLUT2, in combination with other histological stains, revealed distinct features of subcortical structures that are similar to other primates, but also some features that are slightly modified compared to other New World monkeys and other primates. These included subdivisions of the inferior pulvinar, sublamina within the stratum griseum superficiale (SGS) of the superior colliculus, and specific koniocellular layers within the lateral geniculate nucleus. Compared to other New World primates, many features of the subcortical structures that we examined in titi monkeys were most similar to those in owl monkeys and marmosets, with the lateral geniculate nucleus consisting of two main parvocellular layers and two magnocellular layers separated by interlaminar zones or koniocellular layers.

Asunto(s)

Callicebus/anatomía & histología , Colículos Superiores/anatomía & histología , Tálamo/anatomía & histología , Animales , Tronco Encefálico/anatomía & histología , Femenino , Cuerpos Geniculados/anatomía & histología , Inmunohistoquímica , Masculino , Pulvinar/anatomía & histología , Proteína 2 de Transporte Vesicular de Glutamato/metabolismo , Visión Ocular/fisiología

RESUMEN

Lungfishes are the closest living relatives of land vertebrates, and their neuroanatomical organization is particularly relevant for deducing the neural traits that have been conserved, modified, or lost with the transition from fishes to land vertebrates. The immunohistochemical localization of calbindin (CB) and calretinin (CR) provides a powerful method for discerning segregated neuronal populations, fiber tracts, and neuropils and is here applied to the brains of Neoceratodus and Protopterus, representing the two extant orders of lungfishes. The results showed abundant cells containing these proteins in pallial and subpallial telencephalic regions, with particular distinct distribution in the basal ganglia, amygdaloid complex, and septum. Similarly, the distribution of CB and CR containing cells supports the division of the hypothalamus of lungfishes into neuromeric regions, as in tetrapods. The dense concentrations of CB and CR positive cells and fibers highlight the extent of the thalamus. As in other vertebrates, the optic tectum is characterized by numerous CB positive cells and fibers and smaller numbers of CR cells. The so-called cerebellar nucleus contains abundant CB and CR cells with long ascending axons, which raises the possibility that it could be homologized to the secondary gustatory nucleus of other vertebrates. The corpus of the cerebellum is devoid of CB and CR and cells positive for both proteins are found in the cerebellar auricles and the octavolateralis nuclei. Comparison with other vertebrates reveals that lungfishes share most of their features of calcium binding protein distribution with amphibians, particularly with salamanders.

Asunto(s)

Encéfalo/anatomía & histología , Encéfalo/metabolismo , Calbindina 1/metabolismo , Calbindina 2/metabolismo , Peces/anatomía & histología , Acetilcolinesterasa/metabolismo , Animales , Femenino , Masculino , Especificidad de la Especie , Tirosina 3-Monooxigenasa/metabolismo

RESUMEN

Inhibitory neurons are crucial for shaping and regulating the dynamics of the entire network, and disturbances in these neurons contribute to brain disorders. Despite the recent progress in genetic labeling techniques, the heterogeneity of inhibitory neurons requires the development of highly characterized tools that allow accurate, convenient, and versatile visualization of inhibitory neurons in the mouse brain. Here, we report a novel genetic technique to visualize the vast majority and/or sparse subsets of inhibitory neurons in the mouse brain without using techniques that require advanced skills. We developed several lines of Cre-dependent tdTomato reporter mice based on the vesicular GABA transporter (VGAT)-BAC, named VGAT-stop-tdTomato mice. The most useful line (line #54) was selected for further analysis based on two characteristics: the inhibitory neuron-specificity of tdTomato expression and the transgene integration site, which confers efficient breeding and fewer adverse effects resulting from transgene integration-related genomic disruption. Robust and inhibitory neuron-specific expression of tdTomato was observed in a wide range of developmental and cellular contexts. By breeding the VGAT-stop-tdTomato mouse (line #54) with a novel Cre driver mouse line, Galntl4-CreER, sparse labeling of inhibitory neurons was achieved following tamoxifen administration. Furthermore, another interesting line (line #58) was generated through the unexpected integration of the transgene into the X-chromosome and will be used to map X-chromosome inactivation of inhibitory neurons. Taken together, our studies provide new, well-characterized tools with which multiple aspects of inhibitory neurons can be studied in the mouse.

Asunto(s)

Integrasas/metabolismo , Proteínas Luminiscentes/metabolismo , Inhibición Neural/genética , Proteínas del Transporte Vesicular de Aminoácidos Inhibidores/metabolismo , Animales , Encéfalo/citología , Antagonistas de Estrógenos/farmacología , Regulación de la Expresión Génica/genética , Glutamato Descarboxilasa/genética , Glutamato Descarboxilasa/metabolismo , Integrasas/genética , Antígeno Ki-67/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Mutación/genética , N-Acetilgalactosaminiltransferasas/genética , N-Acetilgalactosaminiltransferasas/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Factor de Transcripción PAX2/metabolismo , Proteínas RGS/genética , Proteínas RGS/metabolismo , Somatostatina/metabolismo , Tamoxifeno/farmacología , Proteínas del Transporte Vesicular de Aminoácidos Inhibidores/genética , Polipéptido N-Acetilgalactosaminiltransferasa

RESUMEN

In this review, we outline the history of our current understanding of the organization of the pulvinar complex of mammals. We include more recent evidence from our own studies of both New and Old World monkeys, prosimian galagos, and close relatives of primates, including tree shrews and rodents. Based on cumulative evidence, we provide insights into the possible evolution of the visual pulvinar complex, as well as the possible co-evolution of the inferior pulvinar nuclei and temporal cortical visual areas within the MT complex.

Asunto(s)

Evolución Biológica , Pulvinar/anatomía & histología , Pulvinar/fisiología , Vías Visuales/anatomía & histología , Vías Visuales/fisiología , Percepción Visual/fisiología , Animales , Humanos , Primates

RESUMEN

In songbirds, the learning and maintenance of song is dependent on auditory feedback, but little is known about the presence or role of other forms of sensory feedback. Here, we studied the innervation of the avian vocal organ, the syrinx, in the zebra finch. Using a combination of immunohistochemistry, immunofluorescence and neural tracing with subunit B of cholera toxin (CTB), we analysed the peripheral and central endings of the branch of the hypoglossal nerve that supplies the syrinx, the tracheosyringeal nerve. In the syringeal muscles, we show the presence of numerous choline acetyl transferase-like immunoreactive en plaque motor endplates and substance P-like immunoreactive, thin and varicose free nerve endings. Substance P-like immunoreactive free nerve endings were also present in the luminal syringeal tissues, especially in the luminal epithelium of the trachea and pessulus. Also, by a combination of immunofluorescence and transganglionic tracing following injections of CTB in the tracheosyringeal nerve, we identified as central targets of the syringeal receptors the caudolateral part of the interpolaris subnucleus of the descending trigeminal tract, a caudolateral region of the nucleus tractus solitarius, and a lateral band of the principal sensory trigeminal nucleus. Further studies are required to determine the sensory modalities of these receptors and the connections of their specific synaptic targets.

Asunto(s)

Tronco Encefálico/anatomía & histología , Pinzones/anatomía & histología , Vías Nerviosas/fisiología , Pliegues Vocales/anatomía & histología , Pliegues Vocales/inervación , Animales , Tronco Encefálico/metabolismo , Toxina del Cólera/metabolismo , Colina O-Acetiltransferasa/metabolismo , Nervio Hipogloso/anatomía & histología , Nervio Hipogloso/fisiología , Masculino , Neuronas Motoras/fisiología , Proteínas del Tejido Nervioso/metabolismo , Sustancia P/metabolismo , Vocalización Animal/fisiología

RESUMEN

Our knowledge of the avian sensory trigeminal system has been largely restricted to the principal trigeminal nucleus (PrV) and its ascending projections to the forebrain. Studies addressing the cytoarchitecture and organization of afferent input to the sensory trigeminal complex, which includes both the PrV and the nuclei of the descending trigeminal tract (nTTD), have only been performed in pigeons and ducks. Here we extend such an analysis to a songbird, the zebra finch (Taeniopygia guttata). We describe the cytoarchitecture of the sensory trigeminal complex, the patterns of calbindin-like and substance P-like immunoreactivity, and the organization of afferents from the three branches of the trigeminal nerve and from the lingual branch of the hypoglossal nerve. On the basis of cytoarchitecture and immunohistochemistry, the sensory trigeminal column can be subdivided from caudal to rostral, as in other species, into cervical dorsal horn, subnucleus caudalis, subnucleus interpolaris, subnucleus oralis, and nucleus principalis. The relative positions of the terminal fields of the three trigeminal branches move from medial to lateral in the dorsal horn to dorsomedial to ventrolateral in nTTD, whereas in PrV there is considerable overlap of mandibular and ophthalmic terminal fields, with only a small maxillary input ventrally. The hypoglossal afferents, which terminate medially in the dorsal horn and dorsolaterally in nTTD, terminate in specific cell groups in the dorsolateral nTTDo and in PrV. This work sets the grounds for further analyses of the ascending connections of the nTTD and the afferents from the syrinx to the trigeminal sensory column.

Asunto(s)

Vías Aferentes/fisiología , Mapeo Encefálico , Pinzones/anatomía & histología , Nervio Trigémino/anatomía & histología , Nervio Trigémino/fisiología , Núcleos del Trigémino/anatomía & histología , Animales , Calbindina 1/metabolismo , Toxina del Cólera/metabolismo , Masculino , Sustancia P/metabolismo , Núcleos del Trigémino/fisiología

RESUMEN

The purpose of this work was to evaluate a potentially useful animal model, Meriones shawi (M.sh)-developing metabolic X syndrome, diabetes and possessing a visual streak similar to human macula-in the study of diabetic retinopathy and diabetic macular edema (DME). Type 2 diabetes (T2D) was induced by high fat diet administration in M.sh. Body weights, blood glucose levels were monitored throughout the study. Diabetic retinal histopathology was evaluated 3 and 7 months after diabetes induction. Retinal thickness was measured, retinal cell types were labeled by immunohistochemistry and the number of stained elements were quantified. Apoptosis was determined with TUNEL assay. T2D induced progressive changes in retinal histology. A significant decrease of retinal thickness and glial reactivity was observed without an increase in apoptosis rate. Photoreceptor outer segment degeneration was evident, with a significant decrease in the number of all cones and M-cone subtype, but-surprisingly-an increase in S-cones. Damage of the pigment epithelium was also confirmed. A decrease in the number and labeling intensity of parvalbumin- and calretinin-positive amacrine cells and a loss of ganglion cells was detected. Other cell types showed no evident alterations. No DME-like condition was noticed even after 7 months. M.sh could be a useful model to study the evolution of diabetic retinal pathology and to identify the role of hypertension and dyslipidemia in the development of the reported alterations. Longer follow up would be needed to evaluate the potential use of the visual streak in modeling human macular diseases.

Asunto(s)

Retinopatía Diabética/complicaciones , Degeneración Macular/etiología , Retina/patología , Degeneración Retiniana/etiología , Animales , Apoptosis/fisiología , Modelos Animales de Enfermedad , Gerbillinae , Degeneración Macular/patología , Masculino , Proteínas de Microfilamentos/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Opsinas/metabolismo , Retina/metabolismo , Degeneración Retiniana/patología , Rodopsina/metabolismo , Factor de Transcripción Brn-3A/metabolismo , cis-trans-Isomerasas/metabolismo

RESUMEN

Clinical trials testing the hypothesis that fetal dopamine grafts would provide antiparkinsonian benefit in patients who had already developed side effects from their long-term use of L-dopa revealed, in some cases, the presence of dyskinesias even in the absence of L-dopa. The form, intensity, and frequency of these dyskinesias were quite variable, but their manifestation slowed the clinical development of cell replacement therapies. Rodent models of graft-induced dyskinesias (GIDs) have been proposed, but their accuracy in modeling GIDs has been questioned because they usually require amphetamine for their presentation. The present study attempted to model GIDs in parkinsonian monkeys and, for the first time, to test the effect of grafts on previously dyskinetic monkeys. Toward this end, monkeys were rendered parkinsonian with n-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and dyskinetic with levodopa. They then received intraputamenal grafts of fetal dopaminergic cells, control cerebellar cells, or vehicle bilaterally and were studied for 18 months. Dopaminergic cells were grafted in a manner designed to produce either "hot spot" or "widespread" striatal innervation. Although levodopa-induced dyskinesias could be elicited postoperatively, GIDs were never observed in any animal at any time after grafting. Grafted monkeys were also challenged with levodopa but did not show any greater responses to these challenges than before grafting. These studies support the development of future dopamine neuron cell transplantation therapy-based approaches, indicating that in relevant primate models with appropriate cell preparation methodology, with successful graft survival and putamenal dopamine innervation, there is no evidence of graft-induced dyskinesias. J. Comp. Neurol. 525:498-512, 2017. © 2016 Wiley Periodicals, Inc.

Asunto(s)

Cerebelo/trasplante , Neuronas Dopaminérgicas/trasplante , Discinesia Inducida por Medicamentos/fisiopatología , Trasplante de Tejido Fetal , Intoxicación por MPTP/terapia , Mesencéfalo/trasplante , Neuronas/trasplante , Animales , Antiparkinsonianos/toxicidad , Calbindinas/metabolismo , Núcleo Caudado/patología , Núcleo Caudado/fisiopatología , Cerebelo/metabolismo , Chlorocebus aethiops , Dopamina/administración & dosificación , Dopamina/metabolismo , Canales de Potasio Rectificados Internamente Asociados a la Proteína G/metabolismo , Levodopa/toxicidad , Intoxicación por MPTP/patología , Intoxicación por MPTP/fisiopatología , Masculino , Mesencéfalo/embriología , Mesencéfalo/metabolismo , Microglía/metabolismo , Microglía/patología , Neuronas/metabolismo , Neuronas/patología , Putamen/patología , Putamen/fisiopatología , Putamen/cirugía , Tirosina 3-Monooxigenasa/metabolismo