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Morris Water Maze and Contextual Fear Conditioning Tasks to Evaluate Cognitive Functions Associated With Adult Hippocampal Neurogenesis.

ABSTRACT: New neurons are continuously generated and functionally integrated into the dentate gyrus (DG) network during the adult lifespan of most mammals. The hippocampus is a crucial structure for spatial learning and memory, and the addition of new neurons into the DG circuitry of rodents seems to be a key element for these processes to occur. The Morris water maze (MWM) and contextual fear conditioning (CFC) are among the most commonly used hippocampus-dependent behavioral tasks to study episodic-like learning and memory in rodents. While the functional contribution of adult hippocampal neurogenesis (AHN) through these paradigms has been widely addressed, results have generated controversial findings. In this review, we analyze and discuss possible factors in the experimental methods that could explain the inconsistent results among AHN studies; moreover, we provide specific suggestions for the design of more sensitive protocols to assess AHN-mediated learning and memory functions.

SUBMITTER: Hernandez-Mercado K

PROVIDER: S-EPMC8761726 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:A fundamental question in neuroscience is how memories are stored and retrieved in the brain. Many neurological, psychiatric and neurodevelopmental disorders are associated with cognitive deficits. Therefore characterizing the biological basis of these processes is critical for understanding normal and abnormal brain function. It is known that long-term memory formation requires transcription and translation as well as epigenetic processes that control gene expression. In this study we examined genome-wide gene expression changes during memory consolidation and after memory retrieval. We observe the largest changes in gene expression 30 minutes after memory acquisition and retrieval, and several novel genes were found to be affected by both. Interestingly, acquisition and retrieval of memory down-regulate different processes. Chromatin assembly is down-regulated after memory acquisition whereas RNA processing is down-regulated so after retrieval. Histone variant H2AB levels are reduced following acquisition, while splicing factor Rbfox1 and NMDA receptor-dependent microRNA miR-219 are down-regulated following retrieval. We also show that miR-219 down-regulation after retrieval is accompanied by up-regulation of its target protein CAMKIIÎ³. Our study highlights for the first time the differential involvement of epigenetic mechanisms that control gene expression, such as histone variants and post-transcriptional RNA processing, during memory acquisition and retrieval. 72 total samples were analyzed, including animals trained in a contexual conditioning paradigm (FC) and controls. Tissue was collected at 30 minutes (FC30), 4 hours (FC4), 12 hours (FC12) and 24 hours after FC (FC24) as well as 30 minutes after testing for retrieval of the memory (RT30). Testing was performed at 24 hours after training over a 5-minute interval. Animals that were handled but not trained were dissected at the same time of day to control for variations due to circadian rhythms (CC30, CC4 andCC12). The protocol was repeated over the course of 2 weeks to obtain 9 animals (2 hippocampi) per group, so that 9 independent FC experiments were represented in each time point and all animals for each group were dissected at the exactly the same time of day.

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Morris Water Maze and Contextual Fear Conditioning Tasks to Evaluate Cognitive Functions Associated With Adult Hippocampal Neurogenesis.

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