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1.
Science ; 373(6553)2021 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-34437090

RESUMO

The ability to perceive and respond to environmental stimuli emerges in the absence of sensory experience. Spontaneous retinal activity prior to eye opening guides the refinement of retinotopy and eye-specific segregation in mammals, but its role in the development of higher-order visual response properties remains unclear. Here, we describe a transient window in neonatal mouse development during which the spatial propagation of spontaneous retinal waves resembles the optic flow pattern generated by forward self-motion. We show that wave directionality requires the same circuit components that form the adult direction-selective retinal circuit and that chronic disruption of wave directionality alters the development of direction-selective responses of superior colliculus neurons. These data demonstrate how the developing visual system patterns spontaneous activity to simulate ethologically relevant features of the external world and thereby instruct self-organization.


Assuntos
Fluxo Óptico , Retina/fisiologia , Células Ganglionares da Retina/fisiologia , Visão Ocular/fisiologia , Vias Visuais , Potenciais de Ação , Células Amácrinas/fisiologia , Animais , Animais Recém-Nascidos , Axônios/fisiologia , Proteínas do Citoesqueleto/genética , Camundongos , Movimento (Física) , Mutação , Piridazinas/farmacologia , Receptores de GABA-A/metabolismo , Retina/crescimento & desenvolvimento , Análise Espaço-Temporal , Colículos Superiores/fisiologia
3.
J Clin Lab Anal ; 35(6): e23791, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33955587

RESUMO

BACKGROUND: Tumor-educated platelets (TEPs) may enable blood-based cancer diagnosis. This study aimed to identify diagnostic TEPs genes involved in carcinogenesis. MATERIALS AND METHODS: The TEPs differentially expressed genes (DEGs) between healthy samples and early/advanced cancer samples were obtained using bioinformatics. Gene ontology (GO) analysis and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis were used to identify the pathways and functional annotation of TEPs DEGs. Protein-protein interaction of these TEPs DEGs was analyzed based on the STRING database and visualized by Cytoscape software. The correlation analysis and diagnostic analysis were performed to evaluate the diagnostic value of TEPs mRNAs expression for early/advanced cancers. Quantitative real-time PCR (qRT-PCR) was applied to validate the role of DEGs in cancers. RESULTS: TEPs mRNAs were mostly involved in protein binding, extracellular matrix, and cellular protein metabolic process. RSL24D1 was negatively correlated to early-stage cancers compared to healthy controls and may be potentially used for early cancer diagnosis. In addition, HPSE, IFI27, LGALS3BP, CRYM, HBD, COL6A3, LAMB2, and IFITM3 showed an upward trend in the expression from early to advanced cancer stages. Moreover, ARL2, FCGR2A, and KLHDC8B were positively associated with advanced, metastatic cancers compared to healthy controls. Among the 12 selected DEGs, the expression of 7 DEGs, including RSL24D1, IFI27, CRYM, HBD, IFITM3, FCGR2A, and KLHDC8B, were verified by the qRT-PCR method. CONCLUSION: This study suggests that the 7-gene TEPs liquid-biopsy biomarkers may be used for cancer diagnosis and monitoring.

4.
Cancer Sci ; 112(6): 2140-2157, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33609307

RESUMO

Non-small-cell lung cancer (NSCLC), with its aggressive biological behavior, is one of the most diagnosed cancers. Tumor-associated inflammatory cells play important roles in the interaction between chronic inflammation and lung cancer, however the mechanisms involved are far from defined. In the present study, by developing an orthotopic NSCLC mouse model based on chronic inflammation, we proved that an inflammatory microenvironment accelerated the growth of orthotopic xenografts in vivo. Tumor-associated macrophages, the most abundant population of inflammatory cells, were identified. Treatment with macrophage-conditioned medium (MCM) promoted the growth and migration of NSCLC cells. Using bioinformatics analysis, we identified downregulated PP2Ac expression in NSCLC cells upon treatment with MCM. We further confirmed that this downregulation was executed in an NF-κB pathway-dependent manner. As IκB kinase (IKK) has been proved to be a substrate of PP2Ac, inhibition on PP2Ac could result in amplification of NF-κB pathway signaling. Overexpression of PP2Ac, or the dominant-negative forms of IKK or IκB, attenuated the acceleration of growth and metastasis by MCM. Using bioinformatics analysis, we further identified that CXCL1 and COL6A1 could be downstream of NF-κB/PP2Ac pathway. Luciferase assay and ChIP assay further confirmed the location of response elements on the promoter regions of CXCL1 and COL6A1. Elevated CXCL1 facilitated angiogenesis, whereas upregulated COL6A1 promoted proliferation and migration.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , NF-kappa B/metabolismo , Proteína Fosfatase 2/metabolismo , Macrófagos Associados a Tumor/metabolismo , Animais , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Quimiocina CXCL1/genética , Quimiocina CXCL1/metabolismo , Colágeno Tipo VI/genética , Colágeno Tipo VI/metabolismo , Modelos Animais de Doenças , Progressão da Doença , Retroalimentação Fisiológica , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/metabolismo , Camundongos , Pessoa de Meia-Idade , Neovascularização Patológica , Proteína Fosfatase 2/genética , Transdução de Sinais
5.
Nat Methods ; 17(12): 1262-1271, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33139894

RESUMO

Achieving a comprehensive understanding of brain function requires multiple imaging modalities with complementary strengths. We present an approach for concurrent widefield optical and functional magnetic resonance imaging. By merging these modalities, we can simultaneously acquire whole-brain blood-oxygen-level-dependent (BOLD) and whole-cortex calcium-sensitive fluorescent measures of brain activity. In a transgenic murine model, we show that calcium predicts the BOLD signal, using a model that optimizes a gamma-variant transfer function. We find consistent predictions across the cortex, which are best at low frequency (0.009-0.08 Hz). Furthermore, we show that the relationship between modality connectivity strengths varies by region. Our approach links cell-type-specific optical measurements of activity to the most widely used method for assessing human brain function.


Assuntos
Mapeamento Encefálico/métodos , Proteínas de Ligação ao Cálcio/metabolismo , Córtex Cerebral/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Animais , Gasometria , Cálcio/metabolismo , Proteínas de Ligação ao Cálcio/genética , Fluorescência , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Camundongos , Camundongos Transgênicos , Oxigênio/análise
6.
Neuron ; 104(4): 711-723.e3, 2019 11 20.
Artigo em Inglês | MEDLINE | ID: mdl-31561919

RESUMO

Visual spatial perception in the mammalian brain occurs through two parallel pathways: one reaches the primary visual cortex (V1) through the thalamus and another the superior colliculus (SC) via direct projections from the retina. The origin, development, and relative function of these two evolutionarily distinct pathways remain obscure. We examined the early functional development of both pathways by simultaneously imaging pre- and post-synaptic spontaneous neuronal activity. We observed that the quality of retinal activity transfer to the thalamus and superior colliculus does not change across the first two postnatal weeks. However, beginning in the second postnatal week, retinal activity does not drive V1 as strongly as earlier wave activity, suggesting that intrinsic cortical activity competes with signals from the sensory periphery as the cortex matures. Together, these findings bring new insight into the function of the SC and V1 and the role of peripheral activity in driving both circuits across development.


Assuntos
Neurogênese/fisiologia , Colículos Superiores/fisiologia , Córtex Visual/fisiologia , Vias Visuais/fisiologia , Animais , Feminino , Masculino , Camundongos Endogâmicos C57BL , Colículos Superiores/crescimento & desenvolvimento , Córtex Visual/crescimento & desenvolvimento , Vias Visuais/crescimento & desenvolvimento
7.
Oncol Lett ; 18(1): 571-580, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31289529

RESUMO

Colorectal cancer (CRC) represents the third most common malignancy worldwide. The aim of the present study was to investigate the predictive values of platelet-associated indicators, including platelet count (PLT), plateletcrit (PCT), mean platelet volume (MPV) and platelet distribution width (PDW) in patients with resectable CRC. The current retrospective study included 153 patients who were pathologically diagnosed with resectable CRC. The patients were divided into two groups according to the median value of PLT, PCT, MPV or PDW. To evaluate the changes in PLT, PCT, MPV and PDW following resection and adjuvant chemotherapy, the concept of post-/pre-treatment PLT, PCT, MPV and PDW ratios was introduced, where <1 indicated decreased PLT, PCT, MPV and PDW values after treatment, and where ≥1 suggested stable or increased values. It was revealed that a low MPV prior to treatment correlated with a higher tumor stage. Surgery significantly decreased MPV, but had no impact on PLT, PCT or PDW. Adjuvant chemotherapy significantly decreased PLT and PCT, increased MPV and had no effect on PDW. After the whole course of treatment (surgery combined with adjuvant chemotherapy), PLT, PCT and PDW were significantly decreased. Kaplan-Meier plots illustrated that patients with a post-/pre-treatment MPV ratio <1 had poorer overall survival (OS), whereas the post-/pre-treatment ratios for PLT, PCT and PDW did not correlate with patient outcome. Multivariate Cox regression analysis revealed that sex, tumor size and the post-/pre-treatment MPV ratio were prognostic factors for OS. Therefore, the present results may suggest MPV as a potential prognostic factor in resectable CRC.

8.
Technol Cancer Res Treat ; 18: 1533033819837261, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30871415

RESUMO

BACKGROUND: Lung cancer is the leading cause of cancer death. Platelet-related indictors, including platelet count, plateletcrit, mean platelet volume, and platelet distribution width, not only associate with morphology and functions of platelet but also correlate with tumor development and metastasis. In the present study, we investigated the values of platelet-related indictors in the prognosis evaluation of resectable lung cancers. METHODS: In total, 101 patients with resectable lung cancer were recruited in this study. Patients were divided into 2 groups according to the median pretreatment values. To evaluate the individual value changes after treatment, we introduced the concept of post-/pretreatment ratio (≤1 indicated value was not increased after treatment, while >1 suggested increased value). RESULTS: The high pretreatment platelet count level was correlated with larger tumor size. High pretreatment plateletcrit level was associated with more lymph nodes metastasis. Patients with high pretreatment plateletcrit level had worse overall survival, whereas pretreatment platelet count, mean platelet volume, and platelet distribution width levels were not correlated with outcomes. Surgery had no impact on the values of platelet count, plateletcrit, mean platelet volume, or platelet distribution width. Adjuvant chemotherapy significantly decreased the values of platelet count and plateletcrit, whereas it had no effect on the values of mean platelet volume or platelet distribution width. Whole course of treatment (surgery combined with adjuvant chemotherapy) significantly decreased the values of platelet count and platelet distribution width, whereas it had no effect on the values of plateletcrit or mean platelet volume. Post-/pretreatment platelet count, plateletcrit, mean platelet volume, and platelet distribution width ratios were not correlated with outcomes. Univariate analyses demonstrated that American Joint Committee on Cancer stage and pretreatment plateletcrit level were significant risk factors for prognosis. Cox regression analysis revealed that no factor independently associated with worse survival. CONCLUSION: Pretreatment plateletcrit level could be a potential prognostic factor in resectable lung cancers.


Assuntos
Plaquetas/patologia , Carcinoma Pulmonar de Células não Pequenas/secundário , Neoplasias Pulmonares/patologia , Carcinoma de Pequenas Células do Pulmão/secundário , Plaquetas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/cirurgia , Metástase Linfática , Masculino , Volume Plaquetário Médio , Pessoa de Meia-Idade , Invasividade Neoplásica , Prognóstico , Estudos Retrospectivos , Carcinoma de Pequenas Células do Pulmão/metabolismo , Carcinoma de Pequenas Células do Pulmão/cirurgia , Taxa de Sobrevida
9.
Mol Med Rep ; 19(3): 2330-2340, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30664202

RESUMO

The count and classification of white blood cells (WBCs) may be used as prognostic markers in certain types of cancer. The present study investigated the prognostic potential of the counts of WBCs, including lymphocytes (LYs), monocytes (MOs), neutrophils (NEs), eosinophils (EOs) and basophils (BAs), in the prognosis of resectable colorectal cancer. The present study recruited 153 resectable colorectal cancer cases retrospectively, which were pathologically confirmed. All patients were divided into two groups, according to the median value of LY (low LY, ≤1.632x109/l or high LY, >1.632x109/l), MO (low MO, ≤0.330x109/l or high MO, >0.330x109/l), NE (low NE, ≤3.600x109/l or high NE, >3.600x109/l), EO (low EO, ≤0.085x109/l or high EO, >0.085x109/l), BA (low BA, ≤0.010x109/l or high BA, >0.010x109/l), or WBC (low WBC, ≤5.780x109/l or high WBC, >5.780x109/l). To evaluate the alterations in WBC counts following surgery and adjuvant chemotherapy; all samples received oxiplatin and capecitabine (XELOX) for 6­8 cycles or 5­fluorouracil, leucovorin and oxaliplatin (mFOLFOX6) for 10­12 cycles. XELOX included oxaliplatin administered intravenously at a dose of 130 mg/m2 on day 1 and 850­1,250 mg/m2 capecitabine twice daily for days 1­14, repeated every 3 weeks. mFOLFOX6 included oxaliplatin administered intravenously at a dose of 85 mg/m2, 400 mg/m2 leucovorin and 400 mg/m2 5­FU on day 1 followed by 1,200 mg/m2/days continuous infusion for 2 days (in total, 2,400 mg/m2 over 46­48 h), repeated every 2 weeks. The present study investigated the post/pre­treatment of LY, MO, NE, EO, BA and WBC ratios (≤1 indicated that LY, MO, NE, EO, BA and WBC counts were not increased following therapy; whereas, >1 suggested increased counts). Kaplan­Meier curves were constructed to demonstrate overall survival (OS). A multivariate and univariate logistic regression analyses model was employed to identify the independent risk factors. Low pre­treatment BA counts were associated with larger tumor size (>5 cm); pre­treatment BA levels were positively associated with OS. Surgery significantly decreased the count of BAs and increased the count of EOs; whereas, no effect was observed on LYs, MOs, NEs or WBCs. Adjuvant chemotherapy markedly decreased the counts of LY, NE and WBC; whereas, no notable effects on MOs, EOs or BAs were observed. Whole course treatment (surgery combined with adjuvant chemotherapy) significantly decreased the values of LY, NE and WBC; however, increased the value of EO; no effects on the MO or BA counts were observed. An increased post­/pre­treatment NE ratio suggested poorer prognosis. Multivariate Cox regression analysis revealed that sex, tumor size, pre­treatment BA count and the post­/pre­treatment NE ratio were independent prognostic factors affecting OS. The results of the present study suggested that the pre­treatment BA count and post­/pre­treatment NE ratio may be potential prognostic factors for resectable colorectal cancer.


Assuntos
Neoplasias Colorretais/sangue , Neoplasias Colorretais/tratamento farmacológico , Contagem de Leucócitos , Prognóstico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Basófilos/efeitos dos fármacos , Capecitabina , Quimioterapia Adjuvante , Neoplasias Colorretais/patologia , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Eosinófilos/efeitos dos fármacos , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/análogos & derivados , Humanos , Leucovorina/administração & dosagem , Linfócitos/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Neutrófilos/efeitos dos fármacos , Compostos Organoplatínicos/administração & dosagem , Oxaloacetatos
10.
BMC Gastroenterol ; 18(1): 99, 2018 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-29954326

RESUMO

BACKGROUND: The classifications and counts of white blood cells (WBCs) have been proved to be able to be used as prognostic markers in cancer cases. The present study investigated the potential values of the classifications and counts of WBC, including lymphocyte (LY), monocyte (MO), neutrophil (NE), eosinophil (EO), and basophil (BA) in the prognosis of resectable gastric cancers (GCs). METHODS: This retrospective study recruited 104 resectable GC cases which were pathologically confirmed. The patients were divided into two groups according to the median pre-treatment values. To evaluate the changes in WBC counts and classification after treatment, we introduced the concept of post/pre-treatment ratios (≤ 1 indicated count was not increased after therapy, while > 1 suggested increased count). RESULTS: Pre-treatment NE and total WBC counts were negatively correlated with overall survival (OS). Surgery significantly decreased the level of NE count, but increased the level of EO, whereas had no effect on the levels of LY, MO, BAor total WBC. Adjuvant chemotherapy significantly decreased the level of BA. Whole course of treatment (surgery combined with adjuvant chemotherapy) had no significant effect on the counts of LY, MO, NE, EO, BA or total WBC. Post/pre-treatment ratios of LY, MO NE, EO, BA and total WBC levels had no effects on OS. Univariate analysis indicated that AJCC stage (III) and higher level of pre-treatment total WBC count were prognostic factors affecting OS. Multivariate Cox regression analysis revealed that AJCC stage (III) and higher level of pre-treatment total WBC count were independent prognostic factors. CONCLUSIONS: Pre-treatment NE count and pre-treatment total WBC count may be potential prognostic factors for the prognostic evaluation of GCs.


Assuntos
Neoplasias Gástricas/classificação , Neoplasias Gástricas/imunologia , Adulto , Idoso , Quimioterapia Adjuvante , Feminino , Humanos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Análise de Sobrevida
11.
J Neurosci ; 36(13): 3871-86, 2016 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-27030771

RESUMO

UNLABELLED: Retinal waves are correlated bursts of spontaneous activity whose spatiotemporal patterns are critical for early activity-dependent circuit elaboration and refinement in the mammalian visual system. Three separate developmental wave epochs or stages have been described, but the mechanism(s) of pattern generation of each and their distinct roles in visual circuit development remain incompletely understood. We used neuroanatomical,in vitroandin vivoelectrophysiological, and optical imaging techniques in genetically manipulated mice to examine the mechanisms of wave initiation and propagation and the role of wave patterns in visual circuit development. Through deletion of ß2 subunits of nicotinic acetylcholine receptors (ß2-nAChRs) selectively from starburst amacrine cells (SACs), we show that mutual excitation among SACs is critical for Stage II (cholinergic) retinal wave propagation, supporting models of wave initiation and pattern generation from within a single retinal cell type. We also demonstrate that ß2-nAChRs in SACs, and normal wave patterns, are necessary for eye-specific segregation. Finally, we show that Stage III (glutamatergic) retinal waves are not themselves necessary for normal eye-specific segregation, but elimination of both Stage II and Stage III retinal waves dramatically disrupts eye-specific segregation. This suggests that persistent Stage II retinal waves can adequately compensate for Stage III retinal wave loss during the development and refinement of eye-specific segregation. These experiments confirm key features of the "recurrent network" model for retinal wave propagation and clarify the roles of Stage II and Stage III retinal wave patterns in visual circuit development. SIGNIFICANCE STATEMENT: Spontaneous activity drives early mammalian circuit development, but the initiation and patterning of activity vary across development and among modalities. Cholinergic "retinal waves" are initiated in starburst amacrine cells and propagate to retinal ganglion cells and higher-order visual areas, but the mechanism responsible for creating their unique and critical activity pattern is incompletely understood. We demonstrate that cholinergic wave patterns are dictated by recurrent connectivity within starburst amacrine cells, and retinal ganglion cells act as "readouts" of patterned activity. We also show that eye-specific segregation occurs normally without glutamatergic waves, but elimination of both cholinergic and glutamatergic waves completely disrupts visual circuit development. These results suggest that each retinal wave pattern during development is optimized for concurrently refining multiple visual circuits.


Assuntos
Potenciais de Ação/fisiologia , Células Amácrinas/fisiologia , Regulação da Expressão Gênica no Desenvolvimento/genética , Retina/citologia , Vias Visuais/fisiologia , Potenciais de Ação/efeitos dos fármacos , Fatores Etários , Células Amácrinas/efeitos dos fármacos , Animais , Animais Recém-Nascidos , Cálcio/metabolismo , Toxina da Cólera/metabolismo , Colina O-Acetiltransferase/genética , Colina O-Acetiltransferase/metabolismo , Colinérgicos/farmacologia , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Técnicas In Vitro , Camundongos , Camundongos Transgênicos , Técnicas de Patch-Clamp , Receptores Nicotínicos/deficiência , Receptores Nicotínicos/genética , Retina/efeitos dos fármacos , Retina/crescimento & desenvolvimento , Células Ganglionares da Retina/efeitos dos fármacos , Células Ganglionares da Retina/fisiologia , Proteína Vesicular 1 de Transporte de Glutamato/genética , Proteína Vesicular 1 de Transporte de Glutamato/metabolismo , Vias Visuais/efeitos dos fármacos
12.
Neuron ; 88(3): 565-77, 2015 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-26593093

RESUMO

Unit recordings in behaving animals have revealed the transformation of sensory to motor representations in cortical neurons. However, we still lack basic insights into the mechanisms by which neurons interact to generate such transformations. Here, we study cortical circuits related to behavioral control in mice engaged in a sensory detection task. We recorded neural activity using extracellular and intracellular techniques and analyzed the task-related neural dynamics to reveal underlying circuit processes. Within motor cortex, we find two populations of neurons that have opposing spiking patterns in anticipation of movement. From correlation analyses and circuit modeling, we suggest that these dynamics reflect neural ensembles engaged in a competition. Furthermore, we demonstrate how this competitive circuit may convert a transient, sensory stimulus into a motor command. Together, these data reveal cellular and circuit processes underlying behavioral control and establish an essential framework for future studies linking cellular activity to behavior.


Assuntos
Potenciais de Ação/fisiologia , Objetivos , Córtex Motor/fisiologia , Movimento/fisiologia , Rede Nervosa/fisiologia , Desempenho Psicomotor/fisiologia , Animais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos
13.
Dev Neurobiol ; 75(6): 621-40, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25787992

RESUMO

Spontaneous activity during early development is necessary for the formation of precise neural connections, but it remains uncertain whether activity plays an instructive or permissive role in brain wiring. In the visual system, retinal ganglion cell (RGC) projections to the brain form two prominent sensory maps, one reflecting eye of origin and the other retinotopic location. Recent studies provide compelling evidence supporting an instructive role for spontaneous retinal activity in the development of eye-specific projections, but evidence for a similarly instructive role in the development of retinotopy is more equivocal. Here, we report on experiments in which we knocked down the expression of ß2-containing nicotinic acetylcholine receptors (ß2-nAChRs) specifically in the retina through a Cre-loxP recombination strategy. Overall levels of spontaneous retinal activity in retina-specific ß2-nAChR mutant mice (Rx-ß2cKO), examined in vitro and in vivo, were reduced to a degree comparable to that observed in whole animal ß2-nAChR mouse mutants (ß2KO). However, many residual spontaneous waves in Rx-ß2cKO mice displayed local propagating features with strong correlations between nearby but not distant RGCs typical of waves observed in wild-type (WT) but not ß2KO mice. We further observed that eye-specific segregation was disrupted in Rx-ß2cKO mice, but retinotopy was spared in a competition-dependent manner. These results suggest that propagating patterns of spontaneous retinal waves are essential for normal development of the retinotopic map, even while overall activity levels are significantly reduced, and support an instructive role for spontaneous retinal activity in both eye-specific segregation and retinotopic refinement.


Assuntos
Mapeamento Encefálico , Retina/citologia , Células Ganglionares da Retina/fisiologia , Vias Visuais , Potenciais de Ação/fisiologia , Aminoácidos/metabolismo , Animais , Sinalização do Cálcio/fisiologia , Regulação da Expressão Gênica/genética , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Camundongos , Camundongos Transgênicos , Receptores Nicotínicos/genética , Receptores Nicotínicos/metabolismo , Colículos Superiores , Vias Visuais/citologia , Vias Visuais/embriologia , Vias Visuais/crescimento & desenvolvimento
14.
Neuron ; 84(5): 1049-64, 2014 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-25466916

RESUMO

The elaboration of nascent synaptic connections into highly ordered neural circuits is an integral feature of the developing vertebrate nervous system. In sensory systems, patterned spontaneous activity before the onset of sensation is thought to influence this process, but this conclusion remains controversial, largely due to the inherent difficulty recording neural activity in early development. Here, we describe genetic and pharmacological manipulations of spontaneous retinal activity, assayed in vivo, that demonstrate a causal link between retinal waves and visual circuit refinement. We also report a decoupling of downstream activity in retinorecipient regions of the developing brain after retinal wave disruption. Significantly, we show that the spatiotemporal characteristics of retinal waves affect the development of specific visual circuits. These results conclusively establish retinal waves as necessary and instructive for circuit refinement in the developing nervous system and reveal how neural circuits adjust to altered patterns of activity prior to experience.


Assuntos
Potenciais de Ação/fisiologia , Receptores Nicotínicos/metabolismo , Retina/fisiologia , Vias Visuais/crescimento & desenvolvimento , Fatores Etários , Análise de Variância , Animais , Animais Recém-Nascidos , Cálcio/metabolismo , AMP Cíclico/farmacologia , GMP Cíclico/farmacologia , Inibidores de Ciclo-Oxigenase/farmacologia , Proteínas do Olho/genética , Proteínas do Olho/metabolismo , Lateralidade Funcional , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Técnicas In Vitro , Ácido Meclofenâmico/farmacologia , Camundongos , Camundongos Transgênicos , Fator de Transcrição PAX6 , Fatores de Transcrição Box Pareados/genética , Fatores de Transcrição Box Pareados/metabolismo , RNA Mensageiro/metabolismo , Receptores Nicotínicos/genética , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Retina/citologia , Células Ganglionares da Retina/fisiologia
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