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1.
Brain Struct Funct ; 223(7): 3279-3295, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29869132

RESUMO

In rodents, the medial nucleus of the amygdala receives direct inputs from the accessory olfactory bulbs and is mainly implicated in pheromone-mediated reproductive and defensive behaviors. The principal neurons of the medial amygdala are GABAergic neurons generated principally in the caudo-ventral medial ganglionic eminence and preoptic area. Beside GABAergic neurons, the medial amygdala also contains glutamatergic Otp-expressing neurons cells generated in the lateral hypothalamic neuroepithelium and a non-well characterized Pax6-positive population. In the present work, we describe a novel glutamatergic Ebf3-expressing neuronal subpopulation distributed within the periphery of the postero-ventral medial amygdala. These neurons are generated in a pallial domain characterized by high expression of Gdf10. This territory is topologically the most caudal tier of the ventral pallium and accordingly, we named it Caudo-Ventral Pallium (CVP). In the absence of Pax6, the CVP is disrupted and Ebf3-expressing neurons fail to be generated. Overall, this work proposes a novel model of the neuronal composition of the medial amygdala and unravels for the first time a new novel pallial subpopulation originating from the CVP and expressing the transcription factor Ebf3.


Assuntos
Prosencéfalo Basal/metabolismo , Complexo Nuclear Corticomedial/metabolismo , Fator 10 de Diferenciação de Crescimento/metabolismo , Células-Tronco Neurais/metabolismo , Neurônios/metabolismo , Fatores de Transcrição/metabolismo , Animais , Prosencéfalo Basal/embriologia , Linhagem da Célula , Complexo Nuclear Corticomedial/embriologia , Regulação da Expressão Gênica no Desenvolvimento , Idade Gestacional , Ácido Glutâmico/metabolismo , Fator 10 de Diferenciação de Crescimento/genética , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos ICR , Camundongos Knockout , Fator de Transcrição PAX6/genética , Fator de Transcrição PAX6/metabolismo , Técnicas de Cultura de Tecidos , Fatores de Transcrição/genética
2.
Cereb Cortex ; 27(5): 2841-2856, 2017 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-27178193

RESUMO

A unique population of cells, called "lot cells," circumscribes the path of the lateral olfactory tract (LOT) in the rodent brain and acts to restrict its position at the lateral margin of the telencephalon. Lot cells were believed to originate in the dorsal pallium (DP). We show that Lhx2 null mice that lack a DP show a significant increase in the number of mGluR1/lot cells in the piriform cortex, indicating a non-DP origin of these cells. Since lot cells present common developmental features with Cajal-Retzius (CR) cells, we analyzed Wnt3a- and Dbx1-reporter mouse lines and found that mGluR1/lot cells are not generated in the cortical hem, ventral pallium, or septum, the best characterized sources of CR cells. Finally, we identified a novel origin for the lot cells by combining in utero electroporation assays and histochemical characterization. We show that mGluR1/lot cells are specifically generated in the lateral thalamic eminence and that they express mitral cell markers, although a minority of them express ΔNp73 instead. We conclude that most mGluR1/lot cells are prospective mitral cells migrating to the accessory olfactory bulb (OB), whereas mGluR1+, ΔNp73+ cells are CR cells that migrate through the LOT to the piriform cortex and the OB.


Assuntos
Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Receptores de Glutamato Metabotrópico/metabolismo , Células-Tronco/fisiologia , Tálamo/citologia , Tálamo/metabolismo , Animais , Movimento Celular , Células Cultivadas , Embrião de Mamíferos , Feminino , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Proteínas com Homeodomínio LIM/genética , Proteínas com Homeodomínio LIM/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos ICR , Camundongos Transgênicos , Proteínas do Tecido Nervoso/metabolismo , Neurogênese/fisiologia , Gravidez , Receptores de Glutamato Metabotrópico/genética , Proteínas com Domínio T/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteína Tumoral p73/genética , Proteína Tumoral p73/metabolismo
3.
J Neurosci ; 35(32): 11266-80, 2015 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-26269635

RESUMO

Human mutations in ZIC2 have been identified in patients with holoprosencephaly and schizophrenia. Similarly, Zic2 mutant mice exhibit holoprosencephaly in homozygosis and behavioral and morphological schizophrenic phenotypes associated with forebrain defects in heterozygosis. Despite the devastating effects of mutations in Zic2, the cellular and molecular mechanisms that provoke Zic2-deficiency phenotypes are yet unclear. Here, we report a novel role for this transcription factor in the migration of three different types of forebrain neurons: the Cajal-Retzius cells that populate the surface of the telencephalic vesicles, an amygdaloid group of cells originated in the caudal pole of the telencephalic pallium, and a cell population that travels from the prethalamic neuroepithelium to the ventral lateral geniculate nucleus. Our results also suggest that the receptor EphB1, previously identified as a Zic2 target, may mediate, at least partially, Zic2-dependent migratory events. According to these results, we propose that deficiencies in cell motility and guidance contribute to most of the forebrain pathologies associated with Zic2 mutations. SIGNIFICANCE STATEMENT: Although the phenotype of Zic2 mutant individuals was reported more than 10 years ago, until now, the main function of this transcription factor during early development has not been precisely defined. Here, we reveal a previously unknown role for Zic2 in the migration of forebrain neurons such as Cajal-Retzius cells, interneurons moving to the ventral lateral geniculate nucleus, and neocortical cells going to the amygdala. We believe that the role of this transcription factor in certain populations of migratory cells contributes to defects in cortical layering and hypocellularity in the ventral LGN and amygdala and will contribute to our understanding of the devastating phenotypes associated with Zic2 mutations in both humans and mice.


Assuntos
Movimento Celular/fisiologia , Neurônios/citologia , Prosencéfalo/citologia , Fatores de Transcrição/metabolismo , Animais , Camundongos , Camundongos Transgênicos , Neurônios/metabolismo , Prosencéfalo/metabolismo , Receptor EphB1/genética , Receptor EphB1/metabolismo , Fatores de Transcrição/genética
4.
Nat Rev Neurosci ; 14(3): 202-16, 2013 03.
Artigo em Inglês | MEDLINE | ID: mdl-23385869

RESUMO

A systematic classification and accepted nomenclature of neuron types is much needed but is currently lacking. This article describes a possible taxonomical solution for classifying GABAergic interneurons of the cerebral cortex based on a novel, web-based interactive system that allows experts to classify neurons with pre-determined criteria. Using Bayesian analysis and clustering algorithms on the resulting data, we investigated the suitability of several anatomical terms and neuron names for cortical GABAergic interneurons. Moreover, we show that supervised classification models could automatically categorize interneurons in agreement with experts' assignments. These results demonstrate a practical and objective approach to the naming, characterization and classification of neurons based on community consensus.


Assuntos
Algoritmos , Córtex Cerebral/citologia , Interneurônios/classificação , Interneurônios/citologia , Terminologia como Assunto , Ácido gama-Aminobutírico/metabolismo , Animais , Teorema de Bayes , Córtex Cerebral/metabolismo , Análise por Conglomerados , Humanos , Interneurônios/metabolismo
5.
PLoS One ; 8(1): e53243, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23301049

RESUMO

A definitive consequence of the aging process is the progressive deterioration of higher cognitive functions. Defects in DNA repair mechanisms mostly result in accelerated aging and reduced brain function. DNA polymerase µ is a novel accessory partner for the non-homologous end-joining DNA repair pathway for double-strand breaks, and its deficiency causes reduced DNA repair. Using associative learning and long-term potentiation experiments, we demonstrate that Polµ(-/-) mice, however, maintain the ability to learn at ages when wild-type mice do not. Expression and biochemical analyses suggest that brain aging is delayed in Polµ(-/-) mice, being associated with a reduced error-prone DNA oxidative repair activity and a more efficient mitochondrial function. This is the first example in which the genetic ablation of a DNA-repair function results in a substantially better maintenance of learning abilities, together with fewer signs of brain aging, in old mice.


Assuntos
Envelhecimento , Encéfalo/fisiologia , DNA Polimerase Dirigida por DNA/metabolismo , Aprendizagem , Potenciação de Longa Duração/genética , Animais , Comportamento Animal , Encéfalo/metabolismo , Condicionamento Clássico , DNA/genética , Reparo do DNA , DNA Polimerase Dirigida por DNA/genética , Hipocampo/metabolismo , Locomoção , Masculino , Camundongos , Camundongos Knockout , Estresse Oxidativo , Fenótipo , Reprodutibilidade dos Testes , Temperatura
6.
Front Mol Neurosci ; 5: 76, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22723769

RESUMO

To study the potential role of neural cell adhesion molecule (NCAM) in the development of thalamocortical (TC) axon topography, wild type, and NCAM null mutant mice were analyzed for NCAM expression, projection, and targeting of TC afferents within the somatosensory area of the neocortex. Here we report that NCAM and its α-2,8-linked polysialic acid (PSA) are expressed in developing TC axons during projection to the neocortex. Pathfinding of TC axons in wild type and null mutant mice was mapped using anterograde DiI labeling. At embryonic day E16.5, null mutant mice displayed misguided TC axons in the dorsal telencephalon, but not in the ventral telencephalon, an intermediate target that initially sorts TC axons toward correct neocortical areas. During the early postnatal period, rostrolateral TC axons within the internal capsule along the ventral telencephalon adopted distorted trajectories in the ventral telencephalon and failed to reach the neocortex in NCAM null mutant animals. NCAM null mutants showed abnormal segregation of layer IV barrels in a restricted portion of the somatosensory cortex. As shown by Nissl and cytochrome oxidase staining, barrels of the anterolateral barrel subfield (ALBSF) and the most distal barrels of the posteromedial barrel subfield (PMBSF) did not segregate properly in null mutant mice. These results indicate a novel role for NCAM in axonal pathfinding and topographic sorting of TC axons, which may be important for the function of specific territories of sensory representation in the somatosensory cortex.

8.
Front Neuroanat ; 3: 27, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19949463

RESUMO

The preplate of the cerebral cortex contains projection neurons that connect the cortical primordium with the subpallium. These are collectively named pioneer neurons. After preplate partition, most of these pioneer neurons become subplate neurons. Certain preplate neurons, however, never associate with the subplate but rather with the marginal zone. In the present overview, we propose a novel classification of non-subplate pioneer neurons in rodents into two subtypes. In rats, the neurons of the first subtype are calbindin(+) (CB), calretinin(+) (CR) and L1(+) and are situated in the upper part of the preplate before its partition. Neurons of the second subtype are TAG-1(+) and are located slightly deeper to the previous population in the preplate. After the preplate partition, the CB(+), CR(+) and L1(+) neurons remain in the marginal zone whereas TAG-1(+) neurons become transiently localized in the upper cortical plate. In mice, by contrast, calcium binding proteins did not label pioneer neurons. We define in mice two subtypes of non-subplate pioneer neurons, either L1(+) or TAG-1(+)/cntn2(+). We propose these to be the homologues of the two subtypes of non-subplate pioneer neurons of rats. The anatomical distribution of these neuron populations is similar in rats and mice. The two populations of non-subplate pioneer neurons differ in their axonal projections. Axons of L1(+) pioneer neurons project to the ganglionic eminences and the anterior preoptic area, but avoid entering the posterior limb of the internal capsule towards the thalamus. Axons of TAG-1(+) pioneer neurons project to the lateral parts of the ganglionic eminences at the early stages of cortical histogenesis examined.

9.
Nat Rev Neurosci ; 9(7): 557-68, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18568015

RESUMO

Neuroscience produces a vast amount of data from an enormous diversity of neurons. A neuronal classification system is essential to organize such data and the knowledge that is derived from them. Classification depends on the unequivocal identification of the features that distinguish one type of neuron from another. The problems inherent in this are particularly acute when studying cortical interneurons. To tackle this, we convened a representative group of researchers to agree on a set of terms to describe the anatomical, physiological and molecular features of GABAergic interneurons of the cerebral cortex. The resulting terminology might provide a stepping stone towards a future classification of these complex and heterogeneous cells. Consistent adoption will be important for the success of such an initiative, and we also encourage the active involvement of the broader scientific community in the dynamic evolution of this project.


Assuntos
Córtex Cerebral/citologia , Interneurônios , Ácido gama-Aminobutírico/metabolismo , Potenciais de Ação , Axônios/ultraestrutura , Córtex Cerebral/metabolismo , Humanos , Interneurônios/classificação , Interneurônios/citologia , Interneurônios/metabolismo , Sinapses/ultraestrutura
10.
Cereb Cortex ; 18(7): 1653-63, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18024992

RESUMO

Metabotropic glutamate receptor 1 (mGluR1) has been related to processes underlying learning in hippocampal circuits, but demonstrating its involvement in synaptic plasticity when measured directly on the relevant circuit of a learning animal has proved to be technically difficult. We have recorded the functional changes taking place at the hippocampal CA3-CA1 synapse during the acquisition of an associative task in conscious mice carrying a targeted disruption of the mGluR1 gene. Animals were classically conditioned to evoke eyelid responses, using a trace (conditioned stimulus [CS], tone; unconditioned stimulus [US], electric shock) paradigm. Acquisition of this task was impaired in mutant mGluR1(+/-) mice and abolished in mGluR1(-/-) mice. A single pulse presented to Schaffer collaterals during the CS-US interval evoked a monosynaptic field excitatory postsynaptic potential at ipsilateral CA1 pyramidal cells, whose slope was linearly related to learning evolution in controls but not in mGluR1 mutants. Long-term potentiation evoked by train stimulation of Schaffer collaterals was also impaired in both mGluR1(+/-) and mGluR1(-/-) animals. Administration of the selective mGluR1 antagonist (3aS,6aS)-6a-naphthalen-2-ylmethyl-5-methyliden-hexahydro-cyclopental [c]furan-1-on to wild-type animals mimicked the functional changes associated to mGluR1 insufficiency in mutants. Thus, mGluR1 is required for activity-dependent synaptic plasticity and associative learning in behaving mice.


Assuntos
Aprendizagem por Associação/fisiologia , Comportamento Animal/fisiologia , Hipocampo/fisiologia , Plasticidade Neuronal/fisiologia , Neurônios/fisiologia , Receptores de Glutamato Metabotrópico/metabolismo , Transmissão Sináptica/fisiologia , Animais , Masculino , Camundongos , Camundongos Knockout , Receptores de Glutamato Metabotrópico/genética
11.
Brain Res Rev ; 55(2): 430-44, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17659782

RESUMO

This essay explores the contributions to the organization of neuronal microcircuits in the cerebral cortex by Rafael Lorente de Nó, a renowned disciple of Santiago Ramón y Cajal. Lorente de Nó was impressed by the advances in functional parcellation of the cerebral cortex, and wished to find an anatomical correlate, not in cytoarchitectonic charts but in the fine details of neurons and (soon) of neuronal circuits within a cortical locale. His early analysis culminated in two major papers in 1933 and 1934: he introduced a hypothetical frame in which to integrate circuit anatomical complexity with the ideas on the physiology of the neuron prevalent at the time. In an interlude (1934-1938), Lorente embarked in studies of neuron physiology that inclined him to a reductionist interpretation of the axon as the main functionally relevant entity of neurons. This essay describes my attempts at tracing the links between the master's tradition, the minutiae in the early Golgi studies by Lorente and his concepts of neurophysiology. These are the bases to approach his final synthesis: The cerebral cortex: architecture, intracortical connections and motor projections, published as an invited chapter in J.F. Fulton's "Physiology of the Nervous System" in 1938.


Assuntos
Córtex Cerebral/citologia , Interneurônios/fisiologia , Interneurônios/ultraestrutura , Neuroanatomia/história , Animais , História do Século XIX , História do Século XX , Humanos , Modelos Neurológicos , Rede Nervosa
12.
Proc Natl Acad Sci U S A ; 104(27): 11459-64, 2007 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-17592148

RESUMO

We have studied the role of rostral medial prefrontal cortex (mPFC) on reflexively evoked blinks and on classically conditioned eyelid responses in alert-behaving rabbits. The rostral mPFC was identified by its afferent projections from the medial half of the thalamic mediodorsal nuclear complex. Classical conditioning consisted of a delay paradigm using a 370-ms tone as the conditioned stimulus (CS) and a 100-ms air puff directed at the left cornea as the unconditioned stimulus (US). The CS coterminated with the US. Electrical train stimulation of the contralateral rostral mPFC produced a significant inhibition of air-puff-evoked blinks. The same train stimulation of the rostral mPFC presented during the CS-US interval for 10 successive conditioning sessions significantly reduced the generation of conditioned responses (CRs) as compared with values reached by control animals. Interestingly, the percentage of CRs almost reached control values when train stimulation of the rostral mPFC was removed from the fifth conditioning session on. The electrical stimulation of the rostral mPFC in well conditioned animals produced a significant decrease in the percentage of CRs. Moreover, the stimulation of the rostral mPFC was also able to modify the kinematics (latency, amplitude, and velocity) of evoked CRs. These results suggest that the rostral mPFC is a potent inhibitor of reflexively evoked and classically conditioned eyeblinks but that activation prevents only the expression of CRs, not their latent acquisition. Functional and behavioral implications of this inhibitory role of the rostral mPFC are discussed.


Assuntos
Aprendizagem por Associação/fisiologia , Condicionamento Clássico/fisiologia , Pálpebras/fisiologia , Inibição Neural/fisiologia , Córtex Pré-Frontal/fisiologia , Animais , Estimulação Elétrica , Potenciais Evocados/fisiologia , Coelhos , Reflexo/fisiologia
13.
BMC Dev Biol ; 7: 29, 2007 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-17411441

RESUMO

BACKGROUND: Perlecan is a proteoglycan expressed in the basal lamina of the neuroepithelium during development. Perlecan absence does not impair basal lamina assembly, although in the 55% of the mutants early disruptions of this lamina conducts to exencephaly, impairing brain development. The rest of perlecan-null brains complete its prenatal development, maintain basal lamina continuity interrupted by some isolated ectopias, and are microcephalic. Microcephaly consists of thinner cerebral walls and underdeveloped ganglionic eminences. We have studied the mechanisms that generate brain atrophy in telencephalic areas where basal lamina is intact. RESULTS: Brain atrophy in the absence of perlecan started in the ventral forebrain and extended to lateral and dorsal parts of the cortex in the following stages. First, the subpallial forebrain developed poorly in early perlecan-null embryos, because of a reduced cell proliferation: the number of cells in mitosis decreased since the early stages of development. This reduction resulted in a decreased tangential migration of interneurons to the cerebral cortex. Concomitant with the early hypoplasia observed in the medial ganglionic eminences, Sonic Hedgehog signal decreased in the perlecan-null floor plate basal lamina at E12.5. Second, neurogenesis in the pallial neuroepithelium was affected in perlecan deficient embryos. We found reductions of nearly 50% in the number of cells exiting the cell cycle at E12-E13. The labeling index, which was normal at this age, significantly decreased with advancing corticogenesis. Moreover, nestin+ or PCNA+ progenitors increased since E14.5, reaching up to about 150% of the proportion of PCNA+ cells in the wild-type at E17.5. Thus, labeling index reduction together with increased progenitor population, suggests that atrophy is the result of altered cell cycle progression in the cortical progenitors. Accordingly, less neurons populated the cortical plate and subplate of perlecan-null neocortex, as seen with the neuronal markers beta-tubulin and Tbr1. CONCLUSION: As a component of the basal lamina, perlecan both maintains this structure and controls the response of the neuroepithelium to growth factors. Less mitotic cells in the early medial ganglionic eminences, and impaired cell cycle progression in the late neocortex, suggests insufficient recruitment and signaling by neurogenic morphogens, such as SHH or FGF2.


Assuntos
Proteoglicanas de Heparan Sulfato/genética , Organogênese , Telencéfalo/embriologia , Animais , Apoptose , Membrana Basal/citologia , Membrana Basal/embriologia , Membrana Basal/metabolismo , Contagem de Células , Proliferação de Células , Células-Tronco Embrionárias/citologia , Células-Tronco Embrionárias/metabolismo , Feminino , Maturidade dos Órgãos Fetais , Fator 2 de Crescimento de Fibroblastos/genética , Proteínas Hedgehog/genética , Proteoglicanas de Heparan Sulfato/deficiência , Imuno-Histoquímica , Interneurônios/citologia , Interneurônios/metabolismo , Masculino , Camundongos , Microcefalia/genética , Neocórtex/citologia , Neocórtex/embriologia , Neocórtex/metabolismo , Neurônios/citologia , Neurônios/metabolismo , Gravidez , Telencéfalo/citologia , Telencéfalo/metabolismo
14.
Int J Mol Med ; 18(4): 593-600, 2006 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16964410

RESUMO

We describe a novel spontaneous autosomal recessive mutation, cervelet-4 (crv4), which arose in a BALB/c strain. Mice homozygous for the mutation exhibit principally a reduced body size, a congenital neurological phenotype characterized by ataxic gait and intention tremor, with no gross anomalies observed in brain or cerebellum, and skeletal anomalies. Using linkage analysis, we mapped the crv4 locus to the proximal region of chromosome 10, at the location of the Grm1 gene. Genetic complementation crosses between crv4 and Grm1 KO mice confirmed that crv4 is a new allele of Grm1. Molecular analysis of the Grm1 gene in mutant mice revealed the insertion of a 190-bp LTR fragment in intron 4. Our results also indicated that the presence of the LTR fragment caused the disruption of the Grm1 normal splicing process and complete absence of the wild-type protein. crv4 is an interesting model to extend the study of Grm1 function and the pathological effects of Grm1 deficiency in vivo.


Assuntos
Ataxia/genética , Cifose/genética , Mutação/genética , Splicing de RNA , Receptores de Glutamato Metabotrópico/genética , Escoliose/genética , Animais , Ataxia/etiologia , Sequência de Bases , Western Blotting , Mapeamento Cromossômico/métodos , Modelos Animais de Doenças , Feminino , Genótipo , Humanos , Íntrons/genética , Cifose/complicações , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Dados de Sequência Molecular , Fenótipo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores de Glutamato Metabotrópico/metabolismo , Retroelementos/genética , Escoliose/complicações , Homologia de Sequência do Ácido Nucleico
15.
Hippocampus ; 14(7): 836-48, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15382254

RESUMO

Metabotropic gamma-aminobutyric acid receptors (GABAB) play modulatory roles in central synaptic transmission and are involved in controlling neuronal migration during development. We used immunohistochemical methods to elucidate the expression pattern as well as the cellular and the precise subcellular localization of the GABA(B1a/b) and GABAB2 subunits in the rat hippocampus during prenatal and postnatal development. At the light microscopic level, both GABA(B1a/b) and GABAB2 were expressed in the hippocampal primordium from embryonic day E14. During postnatal development, immunoreactivity for GABA(B1a/b) and GABAB2 was distributed mainly in pyramidal cells, with discrete GABA(B1a/b)-immunopositive cell bodies of interneurons present throughout the hippocampus. Using double immunofluorescence, we demonstrated that during the second week of postnatal development, GABA(B1a/b) but not GABAB2 was expressed in glial cells throughout the hippocampal formation. At the electron microscopic level, GABA(B1a/b) and GABAB2 showed a similar distribution pattern during postnatal development. Thus, at all ages the two receptor subunits were located postsynaptically in dendritic spines and shafts at extrasynaptic and perisynaptic sites in both pyramidal and nonpyramidal cells. We further demonstrated that the two subunits were localized presynaptically along the extrasynaptic plasma membrane of axon terminals and along the presynaptic active zone in both asymmetrical and, to a lesser extent, symmetrical synapses. These results suggest that GABAB receptors are widely expressed in the hippocampus throughout development and that GABA(B1a/b) and GABAB2 form both pre- and postsynaptic receptors.


Assuntos
Hipocampo/crescimento & desenvolvimento , Hipocampo/metabolismo , Receptores de GABA-B/metabolismo , Receptores de Glutamato Metabotrópico/metabolismo , Animais , Animais Recém-Nascidos/fisiologia , Feminino , Imunofluorescência , Hipocampo/embriologia , Técnicas Imunoenzimáticas , Imuno-Histoquímica , Microscopia Confocal , Microscopia Imunoeletrônica , Gravidez , Terminações Pré-Sinápticas/efeitos dos fármacos , Terminações Pré-Sinápticas/metabolismo , Subunidades Proteicas , Células Piramidais/fisiologia , Ratos , Ratos Wistar , Frações Subcelulares/metabolismo
16.
Proc Natl Acad Sci U S A ; 100(21): 12468-73, 2003 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-14523241

RESUMO

Pyramidal neurons of the mammalian cerebral cortex are generated in the ventricular zone of the pallium whereas the subpallium provides the cortex with inhibitory interneurons. The marginal zone contains a subpial stream of migratory interneurons and two different classes of transient neurons, the pioneer neurons provided with corticofugal axons, and the reelin-expressing Cajal-Retzius cells. We found in cultured slices that the medial ganglionic eminence provides the reelin-negative pioneer neurons of the marginal zone. Pioneer neurons sent long projection axons that went through the cortical plate and reached the subplate and the lateral border of the lateral ganglionic eminence. In the cultured slices, pioneer neurons were functionally mature: they displayed a voltage-gated sodium current, expressed functional alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, and showed gamma-aminobutyric acid type A (GABAA) postsynaptic events that were modulated by presynaptic AMPA receptors. Pioneer neurons expressed the adhesion molecules L1 and TAG-1; the latter has been reported to control tangential migrations to the neocortex [Denaxa, M., Chan, C.-H., Schachner, M., Parnavelas, J. & Karagogeos, D. (2001) Development (Cambridge, U.K.) 128, 4635-4644], and we show here that the pioneer neurons of the marginal zone are the cellular substrate of such a function. Finally, we show that, in early corticogenesis, reelin controls both the tangential migration of cortical interneurons toward the cortical plate and the tangential migration of pioneer neurons toward the marginal zone.


Assuntos
Córtex Cerebral/citologia , Córtex Cerebral/embriologia , Células Piramidais/citologia , Animais , Moléculas de Adesão Celular Neuronais/metabolismo , Moléculas de Adesão Celular Neuronais/fisiologia , Diferenciação Celular , Movimento Celular/fisiologia , Córtex Cerebral/fisiologia , Contactina 2 , Técnicas de Cultura , Proteínas da Matriz Extracelular/fisiologia , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Camundongos , Camundongos Knockout , Camundongos Mutantes Neurológicos , Proteínas do Tecido Nervoso , Técnicas de Patch-Clamp , Células Piramidais/fisiologia , Receptores de AMPA/metabolismo , Receptores de GABA-A/metabolismo , Proteína Reelina , Serina Endopeptidases , Canais de Sódio/metabolismo
17.
Eur J Neurosci ; 18(2): 323-32, 2003 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-12887414

RESUMO

We investigated the substrates supporting neuronal migration, and its routes, during early thalamic development in the rat. Neurons and axonal and glial fibres were identified in embryos with single and double immunohistochemistry; dynamic data were obtained with cell tracers in short-term organotypic cultured slices. The earliest thalamic neurons, originating from the ventricular neuroepithelium between embryonic days 13 and 15, include those of the reticular thalamic nucleus. At this developmental stage, calretinin, calbindin or gamma-aminobutyric acid immunostaining revealed both radially and nonradially orientated neurons in the region of reticular thalamic migration, between the dorsal and ventral thalamic primordia. In cultured slices, injections of fluorescent dyes in the neuroepithelium labelled neurons in a migratory stream along radial glia in the same zone. Some labelled fusiform cells departed from this radial trajectory along orthogonal routes within the dorsal thalamus. Confocal microscopy revealed nonradially orientated neurons in close apposition with a fibre system parallel to the lateral thalamic surface. These fibres expressed axonal markers, including the intermediate filament protein alpha-internexin and a polysialylated form of neuronal cell adhesion molecule. Active migration of nonradially orientated neurons along neuronal substrates was confirmed in living cultured slices. In addition, in vitro and ex vivo experiments revealed neurons migrating tangentially in association with glial fibres. These results provide novel evidence that: (i) early generated thalamic neurons follow nonradial routes in addition to glia-linked radial migration; and (ii), nonradially migrating thalamic neurons move along both glial and axonal substrates, which could represent a distinctive feature of thalamic development.


Assuntos
Movimento Celular , Neurônios/citologia , Tálamo/citologia , Tálamo/embriologia , Animais , Biomarcadores , Embrião de Mamíferos , Imuno-Histoquímica , Microscopia Confocal , Molécula L1 de Adesão de Célula Nervosa/metabolismo , Neurônios/fisiologia , Técnicas de Cultura de Órgãos , Ratos , Ratos Sprague-Dawley , Ácidos Siálicos/metabolismo
18.
Brain Res Dev Brain Res ; 140(2): 195-203, 2003 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-12586425

RESUMO

The reelin signaling pathway regulates laminar positioning of radially migrating neurons during cortical development. It has been suggested that reelin secreted by Cajal-Retzius cells in the marginal zone could provide either a stop or an attractant signal for migratory neurons expressing reelin receptors, but the proposed models fail to explain recent experimental findings. Here we provide evidence that the reelin receptor machinery, including the lipoprotein receptors ApoER2 and VLDLR along with the cytoplasmic adaptor protein Dab1, is located in radial glia precursors whose processes span the entire cortical wall from the ventricular zone to the pial surface. Moreover, in reeler mice, defective in reelin, decreased levels of Dab1 in the ventricular zone correspond to an accumulation of the protein in radial end-feet beneath the pia matter. Our results support that neural stem cells receive a functional reelin signal. They are also consistent with a working model of reelin action, according to which reelin signaling on the newborn neuron-inherited radial process regulates perikaryal translocation and positioning.


Assuntos
Moléculas de Adesão Celular Neuronais/fisiologia , Córtex Cerebral/embriologia , Proteínas da Matriz Extracelular/fisiologia , Proteínas do Tecido Nervoso/metabolismo , Neuroglia/metabolismo , Receptores de LDL/metabolismo , Receptores de Lipoproteínas/metabolismo , Animais , Desenvolvimento Embrionário e Fetal/fisiologia , Proteínas Relacionadas a Receptor de LDL , Ratos , Ratos Wistar , Proteína Reelina , Serina Endopeptidases , Distribuição Tecidual
19.
Prog Brain Res ; 136: 281-91, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-12143388

RESUMO

The marginal zone of the developing cerebral cortex is formed by different types of neurons, some of which were described more than one century ago. It is the case of Cajal-Retzius cells, which are known to synthesize and secrete Reelin, an extracellular matrix glycoprotein critically involved in the radial migration and early cortical cytoarchitectonic organization. These cells do not emit projection axons, a characteristic that bespeaks against these cells being considered as pioneer neurons. The true pioneer neurons of the marginal zone are part of a distinct cell entity: these are cells that emit the earliest descending axonal projection from the cerebral cortex into the subpallium, even before than subplate neurons, the other population of pioneer neurons in the cortical anlage. Finally, the marginal zone is a territory where cohorts of undifferentiated cortical interneurons migrate into the upper layers of the cerebral cortex. Marginal zone neurons, including Cajal-Retzius cells, tend to distribute non-uniformly over the cortical surface. Such a mosaic structural configuration points towards more complexities regarding their possible functions during cortical development.


Assuntos
Diferenciação Celular/fisiologia , Movimento Celular/fisiologia , Córtex Cerebral/citologia , Córtex Cerebral/embriologia , Neurônios/citologia , Células-Tronco/citologia , Animais , Axônios/fisiologia , Axônios/ultraestrutura , Moléculas de Adesão Celular Neuronais/metabolismo , Córtex Cerebral/fisiologia , Dendritos/fisiologia , Dendritos/ultraestrutura , Proteínas da Matriz Extracelular/metabolismo , História do Século XIX , História do Século XX , Humanos , Proteínas do Tecido Nervoso , Neuroanatomia/história , Neurônios/fisiologia , Proteína Reelina , Serina Endopeptidases , Células-Tronco/fisiologia
20.
Eur J Neurosci ; 3(2): 118-125, 1991.
Artigo em Inglês | MEDLINE | ID: mdl-12106210

RESUMO

The distribution of the GABAA receptor/benzodiazepine receptor/chloride channel complex was investigated in the thalamus of the rat by means of immunohistochemistry in adulthood, as well as during embryonic and postnatal development, using a monoclonal antibody. In adults, the immunoreactivity for the GABAA receptor complex was intensely expressed by neuronal processes throughout the dorsal thalamus. Neuronal perikaryal membranes were frequently outlined by punctate immunostaining; cell bodies, intrathalamic fibre bundles and the internal capsule did not display immunoreactivity for the GABAA receptor. Regional differences in the expression of the receptor were consistently observed: the immunostaining was much lighter in the thalamic reticular nucleus than in the dorsal thalamic nuclei and, among the latter, the anteroventral nucleus and the ventral nuclear complex displayed the most intense immunopositivity. Immunostaining for the GABAA receptor was already expressed in embryos at E14, and was homogeneously distributed throughout the neuropil of the dorsal and ventral thalamic primordia. During the first two postnatal weeks, a regional differentiation of the immunopositivity was appreciable in the thalamus, with a progressive reduction in the reticular nucleus and a parallel increase in the dorsal thalamic structures. Immunoreactive neuronal perikarya were not observed in the thalamus at any developmental stage. The expression of the GABAA receptor complex appeared to have reached a mature configuration by the end of the third postnatal week. These findings indicate that in adults the GABAA receptor is differentially expressed by thalamic nuclear structures, including the reticular nucleus. Furthermore, the maturation of the receptor in the thalamus undergoes a rearrangement during the first postnatal weeks that results in a considerable regression within the reticular nucleus.

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