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1.
Hippocampus ; 25(11): 1314-26, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-25740272

RESUMEN

New dentate granule cells (GCs) are generated in the hippocampus throughout life. These adult-born neurons are required for spatial learning in the Morris water maze (MWM). In rats, spatial learning shapes the network by regulating their number and dendritic development. Here, we explored whether such modulatory effects exist in mice. New GCs were tagged using thymidine analogs or a GFP-expressing retrovirus. Animals were exposed to a reference memory protocol for 10-14 days (spaced training) at different times after newborn cells labeling. Cell proliferation, cell survival, cell death, neuronal phenotype, and dendritic and spine development were examined using immunohistochemistry. Surprisingly, spatial learning did not modify any of the parameters under scrutiny including cell number and dendritic morphology. These results suggest that although new GCs are required in mice for spatial learning in the MWM, they are, at least for the developmental intervals analyzed here, refractory to behavioral stimuli generated in the course of learning in the MWM.


Asunto(s)
Conducta Animal/fisiología , Fenómenos Fisiológicos Celulares/fisiología , Giro Dentado/citología , Aprendizaje por Laberinto/fisiología , Neurogénesis/fisiología , Neuronas/fisiología , Animales , Femenino , Masculino , Ratones , Ratones Endogámicos C57BL
2.
J Neurosci ; 30(29): 9738-52, 2010 Jul 21.
Artículo en Inglés | MEDLINE | ID: mdl-20660256

RESUMEN

Scribble (Scrib) is a key regulator of apicobasal polarity, presynaptic architecture, and short-term synaptic plasticity in Drosophila. In mammals, its homolog Scrib1 has been implicated in cancer, neural tube closure, and planar cell polarity (PCP), but its specific role in the developing and adult nervous system is unclear. Here, we used the circletail mutant, a mouse model for PCP defects, to show that Scrib1 is located in spines where it influences actin cytoskeleton and spine morphing. In the hippocampus of these mutants, we observed an increased synapse pruning associated with an increased number of enlarged spines and postsynaptic density, and a decreased number of perforated synapses. This phenotype was associated with a mislocalization of the signaling pathway downstream of Scrib1, leading to an overall activation of Rac1 and defects in actin dynamic reorganization. Finally, Scrib1-deficient mice exhibit enhanced learning and memory abilities and impaired social behavior, two features relevant to autistic spectrum disorders. Our data identify Scrib1 as a crucial regulator of brain development and spine morphology, and suggest that Scrib1(crc/+) mice might be a model for studying synaptic dysfunction and human psychiatric disorders.


Asunto(s)
Encéfalo/crecimiento & desarrollo , Hipocampo/citología , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Aprendizaje/fisiología , Memoria/fisiología , Plasticidad Neuronal/genética , Conducta Social , Animales , Encéfalo/embriología , Células COS , Células Cultivadas , Chlorocebus aethiops , Espinas Dendríticas/metabolismo , Espinas Dendríticas/ultraestructura , Femenino , Hipocampo/embriología , Masculino , Ratones , Modelos Animales , Actividad Motora/fisiología , Mutación , Técnicas de Placa-Clamp , Sinapsis/fisiología , Transmisión Sináptica/genética
3.
Cell Stem Cell ; 23(1): 25-30, 2018 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-29681514

RESUMEN

Renewed discussion about whether or not adult neurogenesis exists in the human hippocampus, and the nature and strength of the supporting evidence, has been reignited by two prominently published reports with opposite conclusions. Here, we summarize the state of the field and argue that there is currently no reason to abandon the idea that adult-generated neurons make important functional contributions to neural plasticity and cognition across the human lifespan.


Asunto(s)
Neurogénesis , Plasticidad Neuronal , Neuronas/citología , Adulto , Hipocampo/citología , Humanos
4.
PLoS One ; 3(5): e2245, 2008 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-18493309

RESUMEN

BACKGROUND: Accumulating epidemiological evidence points to the role of genetic background as a modulator of the capacity of adverse early experiences to give rise to mental illness. However, direct evidence of such gene-environment interaction in the context of substance abuse is scarce. In the present study we investigated whether the impact of early life experiences on cocaine intake in adulthood depends on genetic background. In addition, we studied other behavioral dimensions associated with drug abuse, i.e. anxiety- and depression-related behaviors. METHODOLOGY/PRINCIPAL FINDINGS: For this purpose, we manipulated the maternal environment of two inbred mouse strains, the C57BL/6J and DBA/2J by fostering them with non-related mothers, i.e. the C3H/HeN and AKR strains. These mother strains show respectively high and low pup-oriented behavior. As adults, C57BL/6J and DBA/2J were tested either for cocaine intravenous self-administration or in the elevated plus-maze and forced swim test (FST). We found that the impact of maternal environment on cocaine use and a depression-related behavior depends upon genotype, as cocaine self-administration and behavior in the FST were influenced by maternal environment in DBA/2J, but not in C57BL/6J mice. Anxiety was not influenced by maternal environment in either strain. CONCLUSIONS/SIGNIFICANCE: Our experimental approach could contribute to the identification of the psychobiological factors determining the susceptibility or the resilience of certain individuals to develop psychopathologies.


Asunto(s)
Cocaína/administración & dosificación , Exposición Materna , Animales , Conducta Animal , Femenino , Genotipo , Ratones , Ratones Endogámicos , Autoadministración
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