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The Journal of Neuroscience, September 19, 2007, 27(38):10185-10195; doi:10.1523/JNEUROSCI.2757-07.2007

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Cellular/Molecular
Caloric Restriction Increases Learning Consolidation and Facilitates Synaptic Plasticity through Mechanisms Dependent on NR2B Subunits of the NMDA Receptor

Ángela Fontán-Lozano,1 José Luis Sáez-Cassanelli,1 Mari Carmen Inda,1 Mercedes de los Santos-Arteaga,1 Sergio Antonio Sierra-Domínguez,1 Guillermo López-Lluch,2 José María Delgado-García,1 and Ángel Manuel Carrión1

1División de Neurociencias and 2Área de Biología Celular, Universidad Pablo de Olavide de Sevilla, 41013 Sevilla, Spain

Correspondence should be addressed to Dr. Ángel M. Carrión, División de Neurociencias, Universidad Pablo de Olavide, Carretera de Utrera Kilómetro 1, 41013 Sevilla, Spain. Email: amancar{at}upo.es

One of the main focal points of aging research is the search for treatments that will prevent or ameliorate the learning and memory deficiencies associated with aging. Here we have examined the effects of maintaining mature mice on a long-term intermittent fasting diet (L-IFD). We found that L-IFD enhances learning and consolidation processes. We also assessed the long-term changes in synaptic efficiency in these animals. L-IFD mice showed an increase in low-theta-band oscillations, paired-pulse facilitation, and facilitation of long-term synaptic plasticity in the hippocampus with respect to mice fed ad libitum. In addition, we found an increase in the expression of the NMDA receptor subunit NR2B in some brain areas of L-IFD mice. Specific antagonism of this subunit in the hippocampus reversed the beneficial effects of L-IFD. These data provide a molecular and cellular mechanism by which L-IFD may enhance cognition, ameliorating some aging-associated cognitive deficits.

Key words: intermittent fasting diet; learning; consolidation; hippocampus; perirhinal cortex; NMDA receptors; long-term potentiation

Received April 3, 2006; revised Aug. 6, 2007; accepted Aug. 8, 2007.

Correspondence should be addressed to Dr. Ángel M. Carrión, División de Neurociencias, Universidad Pablo de Olavide, Carretera de Utrera Kilómetro 1, 41013 Sevilla, Spain. Email: amancar{at}upo.es






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