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1.
Cereb Cortex ; 30(4): 2573-2585, 2020 04 14.
Artículo en Inglés | MEDLINE | ID: mdl-31800021

RESUMEN

It is generally accepted that formation and storage of memory relies on alterations of the structure and function of brain circuits. However, the structural data, which show learning-induced and long-lasting remodeling of synapses, are still very sparse. Here, we reconstruct 1927 dendritic spines and their postsynaptic densities (PSDs), representing a postsynaptic part of the glutamatergic synapse, in the hippocampal area CA1 of the mice that underwent spatial training. We observe that in young adult (5 months), mice volume of PSDs, but not the volume of the spines, is increased 26 h after the training. The training-induced growth of PSDs is specific for the dendritic spines that lack smooth endoplasmic reticulum and spine apparatuses, and requires autophosphorylation of αCaMKII. Interestingly, aging alters training-induced ultrastructural remodeling of dendritic spines. In old mice, both the median volumes of dendritic spines and PSDs shift after training toward bigger values. Overall, our data support the hypothesis that formation of memory leaves long-lasting footprint on the ultrastructure of brain circuits; however, the form of circuit remodeling changes with age.


Asunto(s)
Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/metabolismo , Espinas Dendríticas/enzimología , Memoria a Largo Plazo/fisiología , Densidad Postsináptica/metabolismo , Animales , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/genética , Espinas Dendríticas/ultraestructura , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Fosforilación/fisiología , Densidad Postsináptica/genética , Densidad Postsináptica/ultraestructura
2.
Addict Biol ; 22(2): 331-341, 2017 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26572936

RESUMEN

The development of addiction is associated with a dysregulation of glutamatergic transmission in the brain reward circuit. α isoform of calcium/calmodulin-dependent kinase II (αCaMKII) is one of the key proteins that regulates structural and functional plasticity of glutamatergic synapses. αCaMKII activity can be controlled by the autophosphorylation of threonine 286. The role of this autophosphorylation in the regulation of addiction-related behaviors has been proposed but is still poorly understood. Here, using αCaMKII autophosphorylation-deficient mutant mice (T286A), we show that, in comparison with wild-type animals, they are less resistant to high doses of alcohol and do not show psychostimulant response neither to alcohol injections nor during voluntary alcohol drinking. T286A mutants are also less prone to develop alcohol addiction-related behaviors including an increased motivation for alcohol, persistent alcohol seeking during withdrawal and alcohol consumption on relapse. Finally, we demonstrate that αCaMKII autophosphorylation regulates also alcohol-induced remodeling of glutamatergic synapses in the hippocampus and amygdala. In conclusion, our data suggest that αCaMKII autophosphorylation-dependent remodeling of glutamatergic synapses is a plausible mechanism for the regulation of the alcohol addiction-related behaviors.


Asunto(s)
Amígdala del Cerebelo/metabolismo , Conducta Animal , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/genética , Depresores del Sistema Nervioso Central/farmacología , Comportamiento de Búsqueda de Drogas , Etanol/farmacología , Hipocampo/metabolismo , Motivación , Alcoholismo/genética , Animales , Femenino , Ácido Glutámico/metabolismo , Masculino , Ratones , Mutación , Fosforilación/genética , Sinapsis/metabolismo
3.
Nutrients ; 14(5)2022 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-35268065

RESUMEN

ß-hydroxy ß-methylbutyrate (HMB), a metabolite of the essential amino acid leucine, has been shown to preserve muscle mass and strength during aging. The signaling mechanism by which HMB elicits its favorable effects on protein metabolism in skeletal muscle is also preserved in the brain. However, there are only a few studies, all at relatively high doses, addressing the effect of HMB supplementation on cognition. This study evaluated the effects of different doses of HMB on the potentiation of hippocampal synapses following the experimental induction of long-term potentiation (LTP) in the hippocampus of behaving rats, as well as on working memory test (delayed matching-to-position, DMTP) in mice. HMB doses in rats were 225 (low), 450 (medium), and 900 (high) mg/kg body weight/day and were double in mice. Rats who received medium or high HMB doses improved LTP, suggesting that HMB administration enhances mechanisms related to neuronal plasticity. In the DMTP test, mice that received any of the tested doses of HMB performed better than the control group in the overall test with particularities depending on the dose and the task phase.


Asunto(s)
Potenciación a Largo Plazo , Memoria a Corto Plazo , Animales , Suplementos Dietéticos , Hipocampo , Ratones , Ratas , Roedores , Valeratos
4.
Front Behav Neurosci ; 8: 140, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24808839

RESUMEN

Repetitive behaviors are a key feature of many pervasive developmental disorders, such as autism. As a heterogeneous group of symptoms, repetitive behaviors are conceptualized into two main subgroups: sensory/motor (lower-order) and cognitive rigidity (higher-order). Although lower-order repetitive behaviors are measured in mouse models in several paradigms, so far there have been no high-throughput tests directly measuring cognitive rigidity. We describe a novel approach for monitoring repetitive behaviors during reversal learning in mice in the automated IntelliCage system. During the reward-motivated place preference reversal learning, designed to assess cognitive abilities of mice, visits to the previously rewarded places were recorded to measure cognitive flexibility. Thereafter, emotional flexibility was assessed by measuring conditioned fear extinction. Additionally, to look for neuronal correlates of cognitive impairments, we measured CA3-CA1 hippocampal long term potentiation (LTP). To standardize the designed tests we used C57BL/6 and BALB/c mice, representing two genetic backgrounds, for induction of autism by prenatal exposure to the sodium valproate. We found impairments of place learning related to perseveration and no LTP impairments in C57BL/6 valproate-treated mice. In contrast, BALB/c valproate-treated mice displayed severe deficits of place learning not associated with perseverative behaviors and accompanied by hippocampal LTP impairments. Alterations of cognitive flexibility observed in C57BL/6 valproate-treated mice were related to neither restricted exploration pattern nor to emotional flexibility. Altogether, we showed that the designed tests of cognitive performance and perseverative behaviors are efficient and highly replicable. Moreover, the results suggest that genetic background is crucial for the behavioral effects of prenatal valproate treatment.

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