Running increases adult neurogenesis and improves pattern separation in various memory tasks including context fear conditioning or touch-screen based spatial learning. However, it is unknown whether pattern separation is improved in spontaneous behavior, not emotionally biased by positive or negative reinforcement. Here we investigated the effect of voluntary running on pattern separation during novel object recognition in mice using relatively similar or substantially different objects.We show that running increases hippocampal neurogenesis but does not affect object recognition memory with 1.5 h delay after sample phase. By contrast, at 24 h delay, running significantly improves recognition memory for similar objects, whereas highly different objects can be distinguished by both, running and sedentary mice. These data show that physical exercise improves pattern separation, independent of negative or positive reinforcement. In sedentary mice there is a pronounced temporal gradient for remembering object details. In running mice, however, increased neurogenesis improves hippocampal coding and temporally preserves distinction of novel objects from familiar ones.
It is well known that the dentate gyrus is critically important for pattern separation within the hippocampal network [1, 2]. Furthermore, it was shown, that adult neurogenesis in the dentate supports pattern separation during hippocampus-dependent memory tasks. This notion is based on the observation that ablation of adult neurogenesis disrupts distinction of similar memories and disturbs differential population coding of similar memory items in the hippocampal CA3 network . For example, animals with intact adult neurogenesis can distinguish similar context during context fear conditioning, closely spaced items on a spatial touch screen or neighboring arms in an 8-arm radial maze . After ablation of adult neurogenesis, however, similar items cannot be distinguished anymore, whereas distinct items, like distinct context, can still be remembered by the animals. Furthermore, newly generated neurons are particularly important during the first 4 weeks after mitosis, as pattern separation in context fear conditioning is most sensitive to manipulations targeted to this young population of granule cells [9, 10]. Interestingly, this time period largely overlaps with a critical period for enhanced synaptic plasticity and synaptic integration of the newly generated young neurons into the hippocampal circuitry . The enhanced plasticity contributes to neuronal pattern separation, as blocking synaptic plasticity in a cohort of newly generated young granule cells (
Physical exercise was reported to increase hippocampal stem cell proliferation and adult neurogenesis . As a consequence hippocampus-dependent learning and memory formation is improved by voluntary wheel running in mice [16, 17]. In particular, pattern separation in a touch screen task was shown to be more precise in running mice as compared to sedentary animals . Remarkably, all the behavioral tests assessing pattern separation used behavioral tasks involving positive (food reward) or negative (electric shock) reinforcement strategies to generate detectable behavioral output. The important contribution of emotions would be consistent with anatomical data, showing extensive hippocampal connectivity with subcortical structures like dorsal raphe, VTA, locus coeruleus, amygdala and nucleus accumbens . Therefore, it is unclear whether improvement in pattern separation is restricted to memory items which are emotionally charged, or whether it generally applies for hippocampus-dependent learning tasks.
For example, it is unknown, whether pattern separation in spontaneous behavior such as Novel Object Recognition (NOR) is also affected by changes in adult neurogenesis. This test is based on the spontaneous tendency of mice to preferentially explore a novel, previously unknown object relative to familiar objects. Thus, no reward or punishment is necessary to be associated with the behavior and the emotional content is minimal. The effect of increasing or decreasing adult neurogenesis on NOR is controversial. Whereas some studies could not detect any impairment in NOR memory after reduction of adult neurogenesis , there was a disruption of NOR memory reported by others [14, 23, 24].
To test effects of physical exercise on pattern separation in a less emotional task, we used a NOR paradigm with different types of objects. We analyzed exploration time of objects which were either similar or very distinct to familiar sample objects. Animals with free access to running wheels were compared to sedentary control animals, showing significant differences in the recognition of similar objects but not distinct objects. This indicates that running significantly improves pattern separation even if the emotional chargeis minimal.