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1.
Nat Neurosci ; 21(7): 920-931, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29915195

RESUMO

Neural circuit assembly relies on the precise synchronization of developmental processes, such as cell migration and axon targeting, but the cell-autonomous mechanisms coordinating these events remain largely unknown. Here we found that different classes of interneurons use distinct routes of migration to reach the embryonic cerebral cortex. Somatostatin-expressing interneurons that migrate through the marginal zone develop into Martinotti cells, one of the most distinctive classes of cortical interneurons. For these cells, migration through the marginal zone is linked to the development of their characteristic layer 1 axonal arborization. Altering the normal migratory route of Martinotti cells by conditional deletion of Mafb-a gene that is preferentially expressed by these cells-cell-autonomously disrupts axonal development and impairs the function of these cells in vivo. Our results suggest that migration and axon targeting programs are coupled to optimize the assembly of inhibitory circuits in the cerebral cortex.


Assuntos
Axônios/fisiologia , Movimento Celular/fisiologia , Córtex Cerebral/fisiologia , Interneurônios/fisiologia , Animais , Córtex Cerebral/citologia , Neurônios GABAérgicos/citologia , Neurônios GABAérgicos/fisiologia , Interneurônios/citologia , Fator de Transcrição MafB/genética , Camundongos Knockout
2.
Cereb Cortex ; 27(2): 933-949, 2017 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-28158484

RESUMO

Neural activity is essential for the maturation of sensory systems. In the rodent primary somatosensory cortex (S1), high extracellular serotonin (5-HT) levels during development impair neural transmission between the thalamus and cortical input layer IV (LIV). Rodent models of impaired 5-HT transporter (SERT) function show disruption in their topological organization of S1 and in the expression of activity-regulated genes essential for inhibitory cortical network formation. It remains unclear how such alterations affect the sensory information processing within cortical LIV. Using serotonin transporter knockout (Sert-/-) rats, we demonstrate that high extracellular serotonin levels are associated with impaired feedforward inhibition (FFI), fewer perisomatic inhibitory synapses, a depolarized GABA reversal potential and reduced expression of KCC2 transporters in juvenile animals. At the neural population level, reduced FFI increases the excitatory drive originating from LIV, facilitating evoked representations in the supragranular layers II/III. The behavioral consequence of these changes in network excitability is faster integration of the sensory information during whisker-based tactile navigation, as Sert-/- rats require fewer whisker contacts with tactile targets and perform object localization with faster reaction times. These results highlight the association of serotonergic homeostasis with formation and excitability of sensory cortical networks, and consequently with sensory perception.


Assuntos
Inibição Neural/fisiologia , Proteínas de Ligação a RNA/metabolismo , Córtex Somatossensorial/fisiologia , Navegação Espacial/fisiologia , Percepção do Tato/fisiologia , Vibrissas/fisiologia , Animais , Espaço Extracelular/metabolismo , Masculino , Potenciais da Membrana/fisiologia , Neurônios/patologia , Neurônios/fisiologia , Proteínas de Ligação a RNA/genética , Ratos Transgênicos , Ratos Wistar , Tempo de Reação/fisiologia , Serotonina/metabolismo , Membro 2 da Família 12 de Carreador de Soluto/metabolismo , Córtex Somatossensorial/patologia , Simportadores/metabolismo , Técnicas de Cultura de Tecidos , Ácido gama-Aminobutírico/metabolismo , Cotransportadores de K e Cl-
3.
Sci Rep ; 6: 34240, 2016 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-27687783

RESUMO

Schizophrenia is a complex disorder that affects cognitive function and has been linked, both in patients and animal models, to dysfunction of the GABAergic system. However, the pathophysiological consequences of this dysfunction are not well understood. Here, we examined the GABAergic system in an animal model displaying schizophrenia-relevant features, the apomorphine-susceptible (APO-SUS) rat and its phenotypic counterpart, the apomorphine-unsusceptible (APO-UNSUS) rat at postnatal day 20-22. We found changes in the expression of the GABA-synthesizing enzyme GAD67 specifically in the prelimbic- but not the infralimbic region of the medial prefrontal cortex (mPFC), indicative of reduced inhibitory function in this region in APO-SUS rats. While we did not observe changes in basal synaptic transmission onto LII/III pyramidal cells in the mPFC of APO-SUS compared to APO-UNSUS rats, we report reduced paired-pulse ratios at longer inter-stimulus intervals. The GABAB receptor antagonist CGP 55845 abolished this reduction, indicating that the decreased paired-pulse ratio was caused by increased GABAB signaling. Consistently, we find an increased expression of the GABAB1 receptor subunit in APO-SUS rats. Our data provide physiological evidence for increased presynaptic GABAB signaling in the mPFC of APO-SUS rats, further supporting an important role for the GABAergic system in the pathophysiology of schizophrenia.

4.
Gen Comp Endocrinol ; 178(1): 116-22, 2012 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-22569169

RESUMO

Classical studies in amphibians have concluded that the endocrine pituitary and pars intermedia are derived from epithelial buccal epidermis and do not require the infundibulum for their induction. These studies also assumed that the pituitary is not subsequently determined by infundibular induction. Our extirpation, auto-transplantation and immunohistochemical studies with Xenopus laevis were initiated to investigate early presumptive pituitary development. These studies were conducted especially with reference to the pars intermedia melanotrope cell's induction, and its production and release of α-melanophore stimulating hormone (α-MSH) from the precursor protein proopiomelanocortin (POMC). Auto-transplantation studies demonstrated that the pituitary POMC-producing cells are determined at a stage prior to pituitary-infundibular contact. The results of experiments involving the extirpation of the presumptive infundibulum also indicated that the infundibulum is not essential for the differentiation of POMC-producing cells. We also demonstrated that early pituitary development involves adherence to the prechiasmatic area of the diencephalon with the pituitary placode growing in a posterior direction toward the infundibulum where contact occurs at Xenopus stage 39/40. Overall, our studies provide a model for early tissue relations among presumptive pituitary, suprachiasmatic nucleus, pars tuberalis and infundibulum during neurulation and later neural tube stages of development. It is hypothesized that the overlying chiasmatic area suppresses pituitary differentiation.


Assuntos
Melanotrofos/citologia , Neuro-Hipófise/crescimento & desenvolvimento , Xenopus laevis/crescimento & desenvolvimento , Animais , Neuro-Hipófise/citologia , Neuro-Hipófise/embriologia , Xenopus laevis/embriologia
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