Enhanced habit-based learning and decreased neurogenesis in the adult hippocampus in a murine model of chronic social stress

Abstract

Stress can induce preferential engagement of habit learning mediated by the basal ganglia, relative to learning that involves complex spatial associations contributed by the hippocampal formation. We explored in mice the influence that chronic episodes of social stress exert on the selection of cognitive/spatial vs. habit-based learning strategies. Male mice were exposed to repeated episodes of social confrontation and were categorized as dominant, subordinate or undetermined according to quantitative ethologically relevant parameters of aggression. Mice were then trained in a conditional discrimination task in the T-maze in the presence of allocentric cues until five correct choices were made. The T-maze was then turned 180 degrees and mice were categorized as "cue-learners" or "place-learners" on the basis of their first response in the probe test. Mice showed a graded preference for place vs. cue learning strategies depending on their social categorization (control>undetermined>dominant>subordinate), which ranged from 55% in controls to only 10% in subordinate mice. The response of subordinate mice differed significantly from controls. Hippocampal neurogenesis was studied in the different groups of mice. In keeping with the tendency to engage habit learning, 2,5-bromodeoxyuridine (BrdU) incorporation in the DG was reduced in mice that experienced agonistic encounters, and so was the expression of doublecortin, a marker for immature neurons. These observations suggest that chronic social stress impairs neurogenesis in the adult hippocampus, weakens spatial learning and strengthens habit-like responses.