Hippocampal plasticity and gene expression underlie object location memory in adolescent and juvenille rats
Date
2017
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Publisher
University of Delaware
Abstract
Novel object recognition (NOR) is a form of incidental learning that relies on a rat’s innate tendency to explore novel stimuli (Dix & Aggleton 1999). Object recognition (OR) is a non-spatial NOR variant that requires rats to learn the identity of objects, resulting in the preferential exploration of a novel object opposed to a familiar object. Object location (OL) evaluates an animal’s ability to learn the spatial location of each object as opposed to its identity by assessing exploration of a moved object. During ontogeny, OR is present as early as Postnatal Day (PD) 17 whereas OL first develops later on PD21 (Westbrook et al., 2014), corresponding with hippocampal maturation. While a number of lesion studies have shown that OL is hippocampus-dependent in adult rats, few have looked at the underlying neuroplastic changes thought to mediate the OL task in developing animals. ☐ The current set of experiments examined the role NMDA receptors (NMDAR) and the upregulation of immediate early genes in developing rats. Experiment 1 found that bilateral microinfusions of MK-801, a non-competitive NMDAR antagonist, into the dorsal hippocampus of adolescent (PD33) rats impairs spatial learning in the OL task, but does not impair learning in the non-spatial OR task. Experiment 2 confirmed in juvenile rats (PD26) that bilateral microinfusions of MK-801 into the dorsal hippocampus also impairs test performance in the OL task. Lastly, Experiment 3 used RT-PCR to examine relative expression of immediate early genes in the dorsal hippocampus and the perirhinal cortex of PD26 rats immediately, 15min, 30min, and 90min post OL testing. We found that hippocampal c-Fos expression was upregulated immediately, 15min, and 90min, while BDNF was upregulated 15min and 90min after testing in comparison to homecage control rats, suggesting a possible modulatory role for these neuroplasticity molecules in spatial learning as it first emerges during ontogeny. In the perirhinal cortex, c-Fos was upregulated immediately, 15min, and 30min after OL testing, while BDNF was only upregulated 15min after OL testing. Taken together, these studies suggest that neuroplastic mechanisms of OL performance in adult rats are evident as early as PD26 in the developing rat.