Neurogenesis and Neural Plasticity (Current Topics in Behavioral Neurosciences)

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In multiple rodent models of HD, environmental enrichment has been shown to ameliorate and delay the onset of both motor and cognitive deficits associated with HD Hockly et al. Additionally, physical activity, and in some cases, environmental enrichment were shown to rescue deficits in BDNF gene expression in mouse models of HD Zajac et al. A stroke occurs when there is poor blood flow to the brain, either through lack of blood flow ischemic stroke or bleeding hemorrhagic , resulting in cell death. Importantly, environmental enrichment has been shown to improve sensorimotor deficits associated with stroke in rodents Janssen et al.

In addition, environmental enrichment has been shown to ameliorate deficits in spatial learning and memory Buchhold et al. Improvements in spatial memory were associated with an increase in hippocampal neurogenesis Wurm et al.

Interestingly, pre-exposure to an enriched environment prior to stroke induction improved the recovery of motor function and spatial learning and memory in stroke animal models as well Xie et al. For example, following focal ischemia, multiple groups of rats were exposed to an enriched rehabilitation therapy six hours a day starting at 5, 14, or 30 days after ischemic stroke Biernaskie et al. Enrichment beginning at day 5 resulted in significant improvements in dendritic growth and complexity within the motor cortex, which correlated with improvements in locomotor function.

Although animals in the day group did not exhibit a change in dendritic growth or complexity, they did demonstrate a modest improvement in behavior.

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Results of this study suggest that a critical period exists after stroke in which the brain is most responsive to the effects of environmental enrichment. Traumatic brain injury TBI is commonly caused by an external force and can lead to both temporary and permanent damage to the brain. In the few examples listed here, environmental enrichment has been shown to positively benefit both cognitive and structural deficits associated with neurodegenerative disease and brain injuries. Importantly, the effects of environmental enrichment extend beyond the hippocampus. While the exact underlying mechanisms through which environmental enrichment works are not fully understood, the benefits are comprehensive, and enrichment represents an extremely effective therapeutic intervention for a wide range of diseases and impairments.

The robust beneficial effects of environmental enrichment in rodents are undeniable and naturally lead to the question of whether this manipulation has relevance to humans. At first glance, the comparison may seem irrelevant, as we already live in an enriched environment compared to the standard laboratory rodent. However, as noted in The Different Components of Environmental Enrichment, even in rodents, it is not clear exactly what aspects of environmental enrichment drive the observed effects and whether these effects would map directly onto humans.

What is clear is that people vary in how much they expose themselves to these environmental enrichments, and the physical and mental changes associated with a wide range of disorders can be affected by enrichment. It is well known that aging is accompanied by memory loss and accelerated cognitive decline. The current consensus in the field is that leading a healthy physical and mentally active lifestyle is beneficial for the brain and body and is the key to successful healthy aging Mora, Supported by the large amount of rodent data that exist demonstrating the positive effects of enriched environment on the cognitive deficits and neurobiological changes associated with aging, an active and all-around healthy lifestyle can be seen as a direct human parallel of environmental enrichment.

In fact, several studies in older adults have shown that engagement in both novel activities Park et al. Although participants demonstrated clear improvements in the cognitive abilities for which they trained, there was only a modest improvement in performance-based measures of daily function. On the face of it, these studies appear to utilize at least some form of enrichment, yet gains were modest at best.

What is NEUROPLASTICITY? What does NEUROPLASTICITY mean? NEURPLASTICITY meaning & definition

Unpacking how an enriched environment influences the animal models may paint a clearer picture of why gains were not larger in humans and what might be done in future studies that attempt to use enrichment more directly as a treatment. Animal models provide us with a vivid understanding of the underlying neurobiology of our brain and how our brain changes with experience. By understanding how our knowledge of animal models translates to humans, perhaps we can gain a better understanding of what a human correlate of environmental enrichment is.

Neurogenesis and hippocampal plasticity in adult brain.

In the following section, we will explore how environmental enrichment relates to humans and we will specifically address this topic from the perspective of animal research. Furthermore, because the impact of environmental enrichment on brain neuroplasticity is so robust, we will specifically focus on human studies that explore the impact of the environment on brain structure and function.

Before we do this, however, it is worth explicitly noting that the studies in humans are necessarily more indirect. We have neither the experimental control over the environmental history in human studies, nor access to the wealth of neurobiological manipulations and measures that we can use in animal models. Thus, the goal of the human studies is often to determine the degree of concordance with findings in animal models rather than to resolutely test the underlying neurobiological mechanisms.

Neuroscience

It can occur in many regions of the brain, and changes in neuroplasticity are often associated with the domain in which learning has occurred. While neuroplasticity cannot be readily observed directly in humans, indirect evidence in the form of changes in magnetic resonance imaging MRI scans designed to assess structure volume, gray matter density, etc. There are even observations of plasticity associated with learning of more abstract knowledge such as medical knowledge Draganski et al. In addition, experts who have mastered specific skills and abilities have been shown to have alterations in the associated brain regions.

Such effects have been observed in musicians Bengtsson et al. We should note that most but not all of these studies suffer from being purely correlational; therefore, we cannot reject the possibility that the differences observed in brain structure were preexisting conditions that enabled individuals to pursue these activities better. Even when viewing these results as examples of neuroplasticity driven by experience, their link to the effects in animal models of environmental enrichment is not entirely clear, given their indirect measures and the unclear mapping between these examples of skill learning and environmental enrichment.

To gain a better understanding of how our knowledge of the environmental enrichment manipulation in animals translates to humans, we will take a closer look at the similarities between humans and animal models. Recognizing these similarities might provide insight into what environmental enrichment is in humans.

As in animals, adult hippocampal neurogenesis exists in humans. The first piece of evidence suggesting that new neurons exist in the hippocampus of humans came from a study of postmortem tissue collected from patients diagnosed with skin cancer Eriksson et al. These patients were treated with BrdU to assess the proliferative activity of the tumorous cells.

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Using immunohistochemistry, BrdU cells co-labeled with the mature neuronal marker NeuN were found near the granule cell layer of the dentate gyrus in the hippocampus in a postmortem histological analysis. This finding suggested that these cells divided at the time of BrdU injection and differentiated into mature neurons. As this study presented a snapshot of neurogenesis at a single time point, it did not address questions as to the dynamics of hippocampal neurogenesis in humans.

At least two other studies have observed dividing cells in the hippocampus using markedly different techniques Manganas et al. A second study observed the age of dividing cells in the hippocampus by measuring concentrations of radioactive carbon 14 C in the genomic DNA of humans who lived during the Cold War Spalding et al. Nuclear bomb testing resulted in a huge increase in atmospheric 14 C, leading to the incorporation of 14 C into the genomic DNA of dividing cells.


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The different concentrations of 14 C in cells corresponded to their time of birth, allowing the retrospective dating of these cells Bergmann et al. These studies are consistent with the idea that, as in other mammals, adult neurogenesis exists in humans; they also serve to highlight the difficulty of carrying out this style of research in humans. As previously discussed see The Different Components of Environmental Enrichment , physical exercise has been singled out as one of the most important components of an enriched environment; it has a particularly robust effect on adult hippocampal neurogenesis.

In a side-by-side study comparing mice and humans, researchers showed that exercise had a similar effect on cerebral blood volume CBV in both humans and mice Pereira et al. In this study, researchers first demonstrated a correlation between exercise-induced CBV and neurogenesis BrdU labeling in the dentate gyrus of animals. Although this study did not directly measure neurogenesis in humans, it provides a powerful side-by-side comparison of humans and animal models and demonstrates similarities in the underlying neurobiology correlating with neurogenesis.

Higher levels of cardiovascular fitness, as measured by V0 2peak , were associated with an increase in hippocampal volume and spatial memory Erickson et al. Importantly, age, sex, and years of education were controlled for in these studies. Figure 2 In older adults, following an aerobic exercise intervention, change in left and right hippocampus volume correlated with A and B aerobic fitness V0 2 max , C and D change in BDNF serum levels, and E and F cognitive improvements in a spatial memory task. Adapted from Erickson et al. To further understand the effects of physical activity on brain neuroplasticity, several studies have performed randomized exercise interventions Colcombe et al.

In a particularly influential study, inactive older adults were recruited for a month physical activity intervention study Figure 2 Erickson et al.


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  5. Participants were randomly distributed into either an active aerobic walking or control stretching group. Following the intervention, participants in the physical activity group showed increases in hippocampal gray matter Fig. Interestingly, when looking at BDNF levels in serum, although researchers did not find an overall increase in BDNF in the physical activity group, they did observe that a greater change in BDNF levels was associated with a greater increase in hippocampal volume Fig. Considering the pivotal role BDNF plays in the interaction between exercise and neurogenesis, these data suggest that exercise-induced changes in BDNF are associated with exercise-induced changes in the hippocampus.

    Several additional studies have examined the effects of physical activity within neurodegenerative clinical populations using randomized intervention studies Krogh et al. Although each of these studies observed an increase in hippocampal gray matter volume, results on symptoms and overall cognition were mixed. Given the close relationship between physical exercise and hippocampal neurogenesis in the rodent model see The Different Components of Environmental Enrichment , the behavioral impact of physical exercise may be more pronounced in more sensitive tasks of behavioral pattern separation.

    In rodents, long-term voluntary wheel-running increased pattern separation performance, an effect that was mediated at least in part by newborn neurons in the hippocampus Creer et al. Although there was no control group, researchers found a positive correlation between a change in V0 2peak and performance in the behavioral pattern separation task.

    Shorter, more acute exercise protocols have also been shown to impact hippocampus-related behavior; however, given the extremely short duration of exercise 10 minutes , these results are more likely to be an effect of exercise independent of hippocampal neurogenesis Basso et al. Importantly, evidence exists to suggest that the hippocampus is also involved in humans during spatial learning, memory, and navigation Maguire et al. Grid- and place-like cells have even been identified in humans Ekstrom et al. As mentioned in The Different Components of Environmental Enrichment, an important aspect of enriched environments is the spatial exploration that the novel environments afford, and exploration of these environments is correlated with neuroplasticity in the hippocampus Freund et al.

    One of the most compelling demonstrations of increased hippocampal neuroplasticity with spatial expertise is the series of experiments performed on London taxi drivers. Obtaining a license as a London taxi cab driver is notoriously difficult and unique among taxi drivers anywhere in the world.

    Neurogenesis and Neural Plasticity : Catherine Belzung :

    The process of obtaining a London taxi driver license can take anywhere from three to four years to complete. Using structural MRI and voxel-based morphology VBM , licensed London taxi drivers were compared with age-, education-, and intelligence-matched controls. Researchers found that the taxi drivers had increased gray matter volumes in the posterior hippocampus region compared to both controls Maguire et al. This increase in gray matter volume correlated with the number of years spent as a taxi driver.

    Structural MRI scans of 79 trainees were taken before and after qualifying for the taxi driver license 39 received their London taxi driver license , and of 31 controls. Cognitive training included visual attention, auditory attention, verbal word lists, working memory, facial memory, logic, spatial memory, and more. Although the studies varied widely in participant number, participant age, type of cognitive intervention, intensity of the physical activity, and length of the intervention, all showed a positive benefit of the intervention on behavior, with a few studies even demonstrating increases in hippocampal cerebral blood flow CBF Consortium, and blood oxygenation level dependent BOLD signal activation in the hippocampus Consortium, ; Rosen et al.

    Results of structural changes in the hippocampus, however, were mixed. However, the physical demands of this intervention were mild. In addition to the complementary effects of environmental enrichment on the underying neurobiology of both humans and animals, several human studies have demonstrated cognitive effects of enrichment which parallel the effects described in animals. The studies presented here support the idea that real-world spatial knowledge is associated with hippocampal neuroplasticity; however, an additional field of spatial research lies within the virtual realm. Importantly, components of the spatial-neural network are active even within these virtual environments, suggesting that, at a very basic level, the hippocampus treats virtual environments with some degree of similarity to real-world environments Ekstrom et al.

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    While virtual environments are often used as a tool to explore spatial memory and the involvement activity of the hippocampus as well as other regions of the medial temporal lobe , a few studies have used these environments to observe a correlation between spatial knowledge and hippocampal volume. When acquiring spatial knowledge of an environment, there are two common strategies used to navigate: a place strategy and a response strategy.

    Place strategies have been shown to rely more on the hippocampus Maguire et al.