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Acta Physiologica Congress

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Acta Physiologica 2012; Volume 204, Supplement 689
91st Annual Meeting of The German Physiological Society
3/22/2012-3/25/2012
Dresden, Germany


INCREASED NR2B/NR2A RATIO IN HIPPOCAMPUS OF SPATIAL LEARNING-IMPAIRED AGED RATS
Abstract number: P291

Tokay1 *T., Rehberg1 M., Rohde1 M., Porath1 K., Kirschstein1 T., Kohling1 R.

1University of Rostock, Institute of Physiology, Rostock, Germany

The activation of the N-methyl-D-aspartate receptor (NMDAR) is critical for the induction of synaptic plasticity in the hippocampus. Aging can alter glutamatergic synaptic transmission in the hippocampus, and cognitive impairments in aged animals are accompanied by reduced NMDAR-mediated plasticity at Schaffer collateral-CA1 synapses. However, the specific contribution of NMDAR subunits to NMDAR-mediated synaptic responses in aged tissue has not yet been fully understood. The main purpose of present study was to examine whether there is an impact of aging on NMDAR subunit expression and whether synaptic plasticity may depend on NMDAR subunit composition in the aged hippocampus. Male adult (3–5 months) and aged (22–26 months) rats were subjected to Morris water maze hidden platform task to evaluate learning and memory ability of animals. Results show that aged rats learnt to find the hidden platform significantly more slowly than adult rats. Consistent with behavioral data, we found a decline of synaptic plasticity at Schaffer collateral-CA1 synapses in aged rats (PTP: 168.2±11.7% of baseline, n=9; LTP: 132.2±10.6% of baseline, n=9) as compared to adult ones (PTP: 241.6±21.9% of baseline; LTP: 163.0±11.9% of baseline, n=12). These electrophysiological data also indicate that, although the aged hippocampus was still capable of producing LTP, the magnitude of which was significantly less than that in adult hippocampus (P < 0.01). We next used intracellular recordings to assess the NMDAR subunit expression in NMDAR-mediated EPSPs (excitatory postsynaptic potentials) in CA1 pyramidal cells. The NMDAR-EPSP after application of the specific NR2A blocker NVP-AAM077 was 32±4% in the adult group versus 51±1% in the aged group (P < 0.01), but after application of the specific NR2B blocker Ro25-6981 the NMDAR-EPSP was reduced to 64±9% in the adult group versus 55±3% in old one (P > 0.05). The calculated EPSP response ratio of NR2B/NR2A was 0.5 in adult rats and 0.9 in aged rats, suggesting an age-related alteration of NMDAR composition in the hippocampus. On the mRNA level, we found similar levels of NR2A transcript abundance in both experimental groups, but significantly increased NR2B transcripts in aged animals. Hence, the quantitative reverse-transcriptase PCR data confirm our electrophysiological results. These results suggest that NR2B subunits are upregulated during aging, while NR2A subunits are unaffected by this process.

To cite this abstract, please use the following information:
Acta Physiologica 2012; Volume 204, Supplement 689 :P291

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