New Brain Cell Formation and Long-Term Memory Enhanced by Running

New study in mice in the inaugural issue of Brain Plasticity reports that new brain cell formation is enhanced by running.

Exercise can enhance the development of new brain cells in the adult brain, a process called adult neurogenesis. These newborn brain cells play an important role in learning and memory. A new study has determined that mice that spent time running on wheels not only developed twice the normal number of new neurons, but also showed an increased ability to distinguish new objects from familiar objects. These results are published in the first issue of Brain Plasticity.

“Our research indicates that exercise-induced increase in neurogenesis improves pattern separation by supporting unique and detailed long-term representations of similar but nevertheless different memory items. Pattern separation is involved in many memory tasks of everyday life. For example, when learning the game of chess, it is critically important to remember the different shapes of pieces like the pawn and bishop. Similarly, remembering the precise pattern of pieces on the board during a previously successful opening or endgame may decide who will win or lose,” explained lead investigator Josef Bischofberger, PhD, Professor, Department of Biomedicine, University of Basel (Switzerland).

“This study provides novel evidence for running-induced enhanced pattern separation. The experiments are based on an innate behavior of mice, which are naturally curious and preferentially explore novel objects in their environment. Objects were designed to be more or less similar to each other, to test how precisely the animals remember object properties. This is unique, in being both not stressful and not requiring additional motivators, such as food or water deprivation, to demonstrate the beneficial effects of exercise on cognition,” commented Brian R. Christie, PhD, Co-Guest Editor of the issue and Professor, Neuroscience Graduate Program Director Division of Medical Sciences, University of Victoria, and Island Medical Program, University of British Columbia.

Professor Bischofberger and co-investigators Stefanie Heigele, PhD, and Leoni Bolz tested two groups of mice, which were housed either without (sedentary) or with running wheels (voluntarily running) using a novel object recognition (NOR) task to assess learning and long-term memory. As rodents prefer to spend more time with novel objects than familiar ones, the researchers first exposed the mice to two identical objects (cones or pyramids, in either black or white). After 1.5 hours, one of the objects was replaced with a new object (cone for pyramid or vice versa) and the mice were observed. After 24 hours elapsed, the new object was again swapped, either with a similar object (same color but different shape) or a distinct object (different color and shape).

After the short 1.5-hour interval, both running and sedentary mice were able to distinguish similar and distinct objects. However, after 24 hours, a difference was observed. Whereas distinct objects were remembered and recognized by both cohorts of mice, only the running mice could faithfully distinguish similar looking objects. Investigators determined therefore that the running mice had developed better pattern separation capabilities than sedentary mice.

To investigate further, the researchers looked for changes in the brains of the mice. By using markers that could identify newly-formed brain cells, they found that running mice developed about twice as many new cells, and those cells had longer dendrites, compared to the sedentary mice, which facilitates the formation of new synaptic contacts between the nerve cells.

“Although running induces both substantial changes in number and morphology of young neurons as well as significant changes in learning behavior, this does not prove a causal relationship,” noted Professor Bischofberger, “Nevertheless, our results, together with previous findings, suggest that the enhanced pattern separation during memory testing is most likely mediated via running-induced increase in adult neurogenesis.”

Image of a rat on a chess board.
As rodents prefer to spend more time with novel objects than familiar ones, the researchers first exposed the mice to two identical objects for habituation (cones or pyramids) and later measured the animals attention towards a novel object with different shape. Credit: Josef Bischofberger, University of Basel.

The precise functional role of new neurons in the hippocampus remains under investigation. However, studies have shown that exercise can improve spatial navigation, contextual memory and the ability to distinguish between highly similar objects or stimuli (pattern separation) in rodents and humans.

“Because exercise can increase the rate of new neurons being produced, it makes it an attractive candidate for therapeutic purposes. Studies have shown that exercise can have both structural and cognitive benefits in rodent models of pathological conditions like Fetal Alcohol Spectrum Disorders (FASD) and Alzheimer’s disease. Thus, increasing neurogenesis is a potential treatment for a variety of disorders that would benefit from improving cognitive capacity. Indeed, studies in humans indicate that exercise can preserve and possibly even enhance cognitive function in individuals with dementia or other forms of mild cognitive impairment,” added Dr. Christie.

About this neuroscience and memory research

The inaugural issue of Brain Plasticity features ten papers that focus on the effects of physical exercise on brain function in animal models. Exercise is a simple, low-cost intervention that promotes cognition and mood, protects against damage associated with neurodegeneration, and may alleviate drug addiction in humans. The mechanisms underlying the beneficial effects of physical activity are the subject of intense investigation. The scientists who have contributed to this issue are working on basic research into the cellular, molecular, and behavioral changes associated with running.

Source: Daphne Watrin – IOS Press
Image Credit: The image is credited to Josef Bischofberger, University of Basel.
Original Research: Full open access research for “Running Improves Pattern Separation during Novel Object Recognition” by Bolz, Leoni, Heigele, Stefanie, and Bischofberger, Josef in Brain Plasticity. Published online October 9 2015 doi:10.3233/BPL-150010


Running Improves Pattern Separation during Novel Object Recognition

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. 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. 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 (<6 weeks post mitosis) by genetic deletion of NR2B receptors strongly reduced context discrimination after context fear conditioning.

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. 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.

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.

“Running Improves Pattern Separation during Novel Object Recognition” by Bolz, Leoni, Heigele, Stefanie, and Bischofberger, Josef in Brain Plasticity. Published online October 9 2015 doi:10.3233/BPL-150010

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