| Abstract No.: | B-B2042 |
| Country: | Canada |
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| Title: | L-TYPE CALCIUM CHANNELS MEDIATE HIPPOCAMPAL LTP IN AGED BUT NOT YOUNG ADULT MICE |
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| Authors/Affiliations: | 1 Julie Robillard*; 1 Brian MacVicar; 2 Brian Christie;
1 University of British Columbia, Vancouver, BC, Canada; 2 University of Victoria, BC, Canada
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| Content: | Objectives: The aging process has a number of effects on the brain, and it has been hypothesized that many age-related changes are mediated by calcium dysregulation. This hypothesis is supported by findings of increased L-type calcium channel activity in the CA1 region of the hippocampus of aged animals. While some studies suggest that this may in turn impact synaptic plasticity in aged animals, the literature for this work is quite disparate as a variety of protocols have been used to elicit LTP in older animals and it is not clear if these different stimulation protocols engage similar mechanisms. The goal of our study is to investigate the ability of different conditioning patterns to elicit LTP in aged mice and to assess the contribution of L-type calcium channels to LTP in these mice.
Materials and Methods: Field recordings from mouse hippocampal brain slices were carried out. Our control adult group consisted of mice aged 1-2 months while our aged animals were 14-20 months. Field excitatory postsynaptic potentials (fEPSPs) were obtained by stimulating the Schaffer collateral-commissural pathway and recording from the stratum radiatum of field CA1. After a minimum of 15 min of stable baseline responses, LTP was induced using a conditioning stimulus (high-frequency stimulation (HFS) or theta-burst stimulation (TBS)). The initial slope of the negative going waveform was used to assess changes in synaptic efficacy. LTP was quantified as the percentage change in individual response slopes collected 55-60 min following the application of the conditioning stimulus, as compared with the average slope of responses acquired prior to the conditioning stimulus. Results: The magnitude of LTP was similar in aged animals compared to adults when using either HFS or TBS. However surprisingly there were remarkable differences in the roles for NMDA receptors versus L-type calcium channels in the young and old mice. The contribution of NMDA receptors and L-type calcium channels to LTP in adult and aged animals was assessed by bath-applying nimodipine, an L-type calcium channel antagonist, or APV, an NMDA receptors antagonist to the slice prior to the conditioning stimulus. In adult animals, nimodipine had no effect, while APV significantly reduced the magnitude of LTP. However we observed the opposite results in aged animals, with APV having no effect and nimodipine significantly reducing the magnitude of LTP.
Conclusion: In conclusion, we report that whereas LTP can be evoked in both young and old mice the cellular mechanisms are dramatically altered by age. Our results demonstrate that a shift occurs whereby HFS-induced LTP arises from NMDAR-dependent mechanisms in adult mice but in aged mice this is an L-type calcium channel-dependent mechanism. |
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