GENETIC BACKGROUND AND AGE INFLUENCE APPETITIVE SPATIAL LEARNING AND DECISION-MAKING IN MICE

Spatial navigation and memory encoding depend on hippocampal neuronal plasticity supported by distributed cortical and subcortical circuits. In mice, hippocampal synaptic plasticity varies across strains and is influenced by age. C57BL/6 mice display congenital presbycusis that can induce cortical reorganization and hippocampal dysfunction, while CBA/CaOla do not exhibit these impairments (doi: 10.1093/cercor/bhaa061). Here, we aimed to scrutinize how mouse strain and age interact to affect behavioural performance in a spatial appetitive learning task.
We trained CBA/CaOlaHsd and C57BL/6 mice in early (2–3 months) or late adulthood (7–8 months) to perform a spatial appetitive T-maze task with rewards available at a fixed location. The task consisted of an initial deterministic phase (100% reward probability) followed by a probabilistic phase (80-30% reward probability). We measured correct choices and latencies across training blocks and combined trial-by-trial metrics with reinforcement learning modelling to assess decision strategies, testing for main effects of Age and Strain as well as their interaction.
Relative to C57BL/6, CBA/CaOla mice displayed lower latencies, reached high performance earlier, and maintained better performance when the reward probability decreased. Age was associated with higher latencies and modulated performance and decision policies in a strain-dependent manner. Moreover, CBA/CaOla displayed higher learning rates from positive outcomes and policies consistent with more robust exploitation under uncertainty, whereas C57BL/6 exhibited stronger omission-driven switching. Together, these findings reveal strain- and age-dependent differences in trial-by-trial decision policies and spatial learning performance.
Supported by a Deutsche Forschungsgemeinschaft grant to DMV and JH (SFB 1280/A04, Project Number: 316803389).