Cognitive, Behavioral, and Systems NeuroscienceResearch PaperYoung hippocampal neurons are critical for recent and remote spatial memory in adult mice
Research Highlights
ā¶Reduced hippocampal neurogenesis impairs recent and remote memory in the spatial water maze whereas performances in the cued Morris water maze task remain intact. ā¶Memory in the object location task is altered when hippocampal neurogenesis is reduced. ā¶Non-spatial recognition memory is insensitive to hippocampal neurogenesis reduction. ā¶Newborn hippocampal neurons aged between 1 and 2 weeks are required for hippocampal-dependent forms of memory.
Section snippets
Animals and housing conditions
Adult male C57BL/6 mice (9 week-old, Charles River Laboratories, OrlƩans, France) were housed in fours in a temperature-controlled animal facility with a 12 h light/dark cycle and had access to food and water ad libitum. All experiments were performed in strict accordance with the recommendations of the European Union and the French National Committee (86/609/EEC).
BrdU injections and MAM treatment
We first identified a dose for MAM administration in mice that reduced neurogenesis in the hippocampus, without affecting general
Hippocampal neurogenesis is reduced by MAM treatment during behavioral tests
Mice were sacrificed after completion of the behavioral tests (day 22), when BrdU-labeled (BrdU+) cells were 10 to 11 days old (Fig. 1A). Quantification of double-labeled BrdU+/NeuN+ cells revealed that the dentate gyrus of MAM-treated mice contained a significantly lower number of new neurons (368.1Ā±86.4) compared to control mice (896.6Ā±107.6) (F(1,15)=14.192; P<0.01; Fig. 1B, C). Thus, the subchronic treatment with MAM reduced by 59% the population of hippocampal neurons younger than 14 days
Discussion
In the present study we report that a reduced number of young hippocampal neurons leads to memory impairment depending both on the type of task (spatial vs. non-spatial) and on the task's dependence on the hippocampus (dependent vs. independent). Our findings demonstrate that spatial hippocampal-dependent types of memory are vulnerable to a partial reduction of adult neurogenesis.
To reduce neurogenesis in the hippocampus, we used the cytostatic agent MAM which reversibly stops progenitor cells
Conclusion
Altogether, our findings support the idea that newborn hippocampal neurons aged between 1 and 14 days are required for hippocampal-dependent forms of memory. These data are in agreement with our recent report that new neurons contribute to remote spatial memory retrieval (Trouche et al., 2009) and further point out that they are critically involved in recent spatial memory. Although adult-generated granular neurons represent only a small population of cells within the adult dentate gyrus,
Acknowledgments
We warmly thank HĆ©lĆØne Halley for her technical help and Bernard FrancĆØs for his advice. This work was supported by grants from the Agence Nationale pour la Recherche (ANR-06-NEURO-027) and the EU Frameworkprogram 6 (Integrated project PROMEMORIA 512012) to C.R., by the CNRS and Toulouse University.
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Functional neuroanatomy of allocentric remote spatial memory in rodents
2022, Neuroscience and Biobehavioral ReviewsCitation Excerpt :We selected this period of time to reduce variability, and we distinguished between mice and rats. Under these criteria, we found a total of 25 studies, of which 23 used the MWM (92%) (Barry et al., 2016; Bonaccorsi et al., 2013; Broadbent et al., 2006; Carr et al., 2016; Fremouw et al., 2012; Goodman et al., 2010; Gusev et al., 2005; Gusev and Gubin, 2010b, 2010a; Haijima and Ichitani, 2008; Hales et al., 2018; Kim et al., 2018; Klein et al., 2019; Li et al., 2008; Lopez et al., 2009; Loureiro et al., 2012; Teixeira et al., 2006; Tong et al., 2015; Trouche et al., 2009; Wartman and Holahan, 2014; White et al., 2008; Zorzo et al., 2020), while two of them selected the RAM (8%) (Ramos, 2009; Sebastian et al., 2013). All of the studies showed good retrieval, except for two (Carr et al., 2016; Ramos, 2009), one for each behavioral task.
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These authors contributed equally to this work.