Receptor mechanisms underlying neuronal survival in adult-generated dentate gyrus granule cells




Harris, Stacie R.

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Adult neurogenesis occurs in the dentate gyrus (DG) of the hippocampus a structure well investigated and related to memory consolidation (Altman et al., 1965). Preliminary studies in our lab show low-frequency stimulation (LFS) of the medial perforant pathway confers survival of 8-day-old GC neurons, possibly due to the appearance and activation of local receptors. I hypothesize that activation of either GABAa or NR2B NMDA receptors by ambient GABA or glutamate underlies afferent activity-mediated neuronal survival. Contrary to preliminary studies showing survival following LFS, the LFS treated saline control group in the receptor study did not reveal any significant increases in survival. Therefore, although survival with GABAa and NR2B NMDA antagonist with LFS was equivalent to controls suggesting the antagonists blocked survival, it is not possible to interpret the requirement for these receptors mediating survival following LFS. Due to conflicting data, I replicated LFS experiments including a group to control for exposing animals to the lab and attachment to the recording apparatus. The results showed a significant increase in survival for rats receiving LFS and unstimulated rats connected to the stimulation setup. I conclude that LFS is not necessary to elicit survival of 8 day old cells, but rather a survival increase may be a result of a single exposure to a novel context. To test my hypothesis I exposed rats to the stimulation setup without any connection to the recording device for ninety minutes and the results show increased survival compared to controls which were only transported to the lab. Unusual variability was shown in individual cell counts across groups in the novelty study. Further investigations will study the effects of a single exposure of novelty on dentate granule cell survival.


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Adult Neurogenesis, GABAa receptors, Low Freqency Stimulation, Novelty, NR2B NMDA receptors



Integrative Biology