Consistent within-group covariance of septal and temporal hippocampal neurogenesis with behavioral phenotypes for exploration and memory retention across wild and laboratory small rodents

Abstract

Striking differences in the septo-temporal distribution of neurogenesis are found in small rodents. Here, we assessed the association of adult hippocampal neurogenesis with behavioral responses to novelty, temporal and spatial sequence and reversal learning in wild, wild-derived and laboratory rodents using an automated testing apparatus, the IntelliCage. Behaviorally, DBA/2 and wild-derived house mice were quickest to explore a novel environment, wild wood mice and bank voles were slowest, and C57BL/6 intermediate. Rule learning (temporal and spatial) was fastest in wood mice and bank voles, while DBA/2 and house mice performed poorer. C57BL/6 performed similar to the house mice in the temporal task and similar to wild rodents in the spatial task. Using the number of DCX-positive neurons and proliferating, Ki67-positive cells in the septal, intermediate and temporal hippocampus as a proxy, an ANCOVA was used to test for within-group relations between neurogenesis and behavior. We found that higher numbers of DCX-positive cells in the temporal hippocampus were associated with an increased latency and a lower frequency to explore a novel environment. Temporal and spatial sequence learning was not associated with neurogenesis. In the spatial reversal task however, animals with higher septal neurogenesis showed a persevering phenotype and slower re-learning. Our findings provide strong evidence of septo-temporally segregated neurogenesis effects on behavior across five rodent strains and species. While temporal neurogenesis covaries with behavioral responses to novelty, septal neurogenesis relates to perseverance of a successfully learned spatial rule. Importantly, these associations were independent of species or strain and can be found in both wild and domesticated rodents.