The broad goal of this project is to determine the involvement of adult hippocampal neurogenesis in hippocampal-dependent learning and memory. It has been shown that the dentate gyrus of the hippocampus has the ability to produce new neurons into adulthood. Many of these newborn cells mature into dentate granule neurons with functional synapses. Previous literature showed that ablation of hippocampal neurogenesis in rodents inhibits the behavioral response to antidepressant drugs and led to the hypothesis that neurogenesis is required for the therapeutic action of antidepressant drugs. Conversely, arresting neurogenesis impairs several forms of hippocampus-dependent learning. We have shown that blocking hippocampal neurogenesis using x-irradiation or an inducible genetic ablation method impairs contextual fear conditioning but improves a working memory task, novel object recognition. Furthermore, arrest of neurogenesis using these methods eliminates a form of long term potentiatioh (LTP) in the medial perforant path, termed ACSF-LTP. In consideration of evidence that developing adult-born neurons exhibit unique physiological properties, the proposed research will use contextual fear conditioning, novel object recognition, and electrophysiology (ACSF-LTP) to determine at what age adult-bom neurons become necessary for these hippocampal-dependent tasks.
Hippocampal neurogenesis has been shown to influence specific learning paradigms as well as antidepressant responses. Strategies aimed at stimulating hippocampal neurogenesis could provide novel avenues for the treatment of cognitive and mood disorders.
|Denny, Christine A; Kheirbek, Mazen A; Alba, Eva L et al. (2014) Hippocampal memory traces are differentially modulated by experience, time, and adult neurogenesis. Neuron 83:189-201|
|Denny, Christine A; Burghardt, Nesha S; Schachter, Daniel M et al. (2012) 4- to 6-week-old adult-born hippocampal neurons influence novelty-evoked exploration and contextual fear conditioning. Hippocampus 22:1188-201|
|Drew, Michael R; Denny, Christine A; Hen, Rene (2010) Arrest of adult hippocampal neurogenesis in mice impairs single- but not multiple-trial contextual fear conditioning. Behav Neurosci 124:446-54|