Is there a link between adult neurogenesis and learning?

Leuner, Benedetta; Gould, Elizabeth; Shors, Tracey J.

doi:10.1002/hipo.20153

Cited by 477 publications

(361 citation statements)

References 100 publications

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“…Several lines of evidence support this hypothesis: (i) strong correlation between the rate of neurogenesis and spatial learning in the water maze among mice inbred strains 61 and in old rats from an outbreed strain. 62 (ii) manipulations in which inhibiting hippocampal neurogenesis resulted in hippocampus-dependent learning deficits; 32,45,63 and (iii) observations that learning itself can enhance the survival rate of new hippocampal neurons, [64][65][66] and induce apoptosis of more immature cells and proliferation of neural precursors. 67 However, other studies found the opposite (that is negative) correlation between the rate of hippocampal cell proliferation and spatial learning 68 or failed to find deficits in hippocampus-dependent learning after ablation of hippocampal neurogenesis.…”

Section: Discussionmentioning

confidence: 99%

Macrophage migration inhibitory factor is critically involved in basal and fluoxetine-stimulated adult hippocampal cell proliferation and in anxiety, depression, and memory-related behaviors

et al. 2010

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Intensive research is devoted to unravel the neurobiological mechanisms mediating adult hippocampal neurogenesis, its regulation by antidepressants, and its behavioral consequences. Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine that is expressed in the CNS, where its function is unknown. Here, we show, for the first time, the relevance of MIF expression for adult hippocampal neurogenesis. We identify MIF expression in neurogenic cells (in stem cells, cells undergoing proliferation, and in newly proliferated cells undergoing maturation) in the subgranular zone of the rodent dentate gyrus. A causal function for MIF in cell proliferation was shown using genetic (MIF gene deletion) and pharmacological (treatment with the MIF antagonist Iso-1) approaches. Behaviorally, genetic deletion of MIF resulted in increased anxiety-and depression-like behaviors, as well as of impaired hippocampus-dependent memory. Together, our studies provide evidence supporting a pivotal function for MIF in both basal and antidepressant-stimulated adult hippocampal cell proliferation. Moreover, loss of MIF results in a behavioral phenotype that, to a large extent, corresponds with alterations predicted to arise from reduced hippocampal neurogenesis. These findings underscore MIF as a potentially relevant molecular target for the development of treatments linked to deficits in neurogenesis, as well as to problems related to anxiety, depression, and cognition.

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Section: Discussionmentioning

confidence: 99%

Macrophage migration inhibitory factor is critically involved in basal and fluoxetine-stimulated adult hippocampal cell proliferation and in anxiety, depression, and memory-related behaviors

et al. 2010

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“…At the level of the dentate gyrus, regulation of synaptic connectivity extends beyond changes in the number and strength of synapses, to the de novo addition of new neurons in adulthood 9 . Data from studies of animal models suggest impairment of both synaptic plasticity and adult neurogenesis in diabetes.…”

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confidence: 99%

Diabetes impairs hippocampal function through glucocorticoid-mediated effects on new and mature neurons

et al. 2008

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Multiple organ systems are adversely affected by diabetes, including the brain, which undergoes changes that may increase the risk of cognitive decline. Although diabetes influences the hypothalamic-pituitary-adrenal axis, the role of this neuroendocrine system in diabetes-induced cognitive dysfunction remains unexplored. Here we demonstrate that, in both insulin-deficient rats and insulin-resistant mice, diabetes impairs hippocampus-dependent memory, perforant path synaptic plasticity and adult neurogenesis, and the adrenal steroid corticosterone contributes to these adverse effects. Rats treated with streptozocin have reduced levels of insulin, and exhibit hyperglycemia, increased levels of corticosterone, and impairments in hippocampal neurogenesis, synaptic plasticity and learning. Similar deficits are observed in db/db mice, which are characterized by insulin resistance, elevated corticosterone levels and obesity. Changes in hippocampal plasticity and function in both models are reversed when normal physiological levels of corticosterone are maintained, suggesting that cognitive impairment in diabetes may result from glucocorticoidmediated deficits in neurogenesis and synaptic plasticity. Keywords glucocorticoid; dentate gyrus; streptozotocin; water maze; object recognition As a result of high calorie diets and sedentary lifestyles, diabetes is rapidly becoming more prevalent in Western societies 1 . In addition to its well-known adverse effects on the cardiovascular and peripheral nervous systems, diabetes also appears to negatively impact the brain, increasing the risk of depression and dementia2 , 3 . Human subjects with either type 1 (caused by insulin deficiency) or type 2 (mediated by insulin resistance) diabetes typically exhibit impaired cognitive function compared to age-matched non-diabetic subjects 3,4 . Cognitive deficits have also been documented in studies of rodent models of diabetes. For Supplementary Information accompanies this paper.Competing interests statement. The authors declare that they have no competing financial interests. Conflict of Interest:The authors declare no conflict of interest. NIH Public Access Author ManuscriptNat Neurosci. Author manuscript; available in PMC 2010 August 25. Published in final edited form as:Nat Neurosci. 2008 March ; 11(3): 309-317. doi:10.1038/nn2055. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript example, rats rendered diabetic by treatment with the pancreatic β-cell toxin streptozocin (STZ; a model of type 1 diabetes) exhibit impaired performance in tests of spatial learning ability 5, 6. Similar deficits have been reported in the db/db mouse7, a model of Type 2 diabetes in which obesity, hyperglycemia, and elevations in circulating corticosterone levels arise from a mutation that inactivates the leptin receptor 8 . However, the mechanism(s) responsible for cognitive dysfunction in diabetes has not been established.Within the hippocampus, changes in the strength of synapses between groups of neurons play a critic...

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“…This phenomenon has received widespread attention because of its perceived role in functions such as learning, memory, and mood (Aimone et al 2006;Clelland et al 2009;Drapeau et al 2003;Dupret et al 2007;Eisch et al 2008;Imayoshi et al 2008;Jessberger et al 2009;Kee et al 2007;Kuhn et al 1996;Leuner et al 2006;Sahay and Hen 2007;Santarelli et al 2003). However, the extent of neurogenesis progressively declines with age resulting in~90 % decline in old age (Kuhn et al 1996;Rao et al 2005Rao et al , 2006.…”

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confidence: 99%

Neural stem cell- and neurogenesis-related gene expression profiles in the young and aged dentate gyrus

Shetty

Hattiangady

Shetty

2013

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Hippocampal neurogenesis, important for memory and mood function, wanes greatly in old age. Studies in rat models have implied that this decrease is not due to loss of neural stem cells (NSCs) in the subgranular zone of the dentate gyrus (DG) but rather due to an increased quiescence of NSCs. Additional studies have suggested that changes in the microenvironment, particularly declines in the concentrations of neurotrophic factors, underlie this change. In this study, we compared the expression of 84 genes that are important for NSC proliferation and neurogenesis between the DG of young (4 months old) and aged (24 months old) Fischer 344 rats, using a quantitative real-time polymerase chain reaction array. Interestingly, the expression of a vast majority of genes that have been reported previously to positively or negatively regulate NSC proliferation was unaltered with aging. Furthermore, most genes important for cell cycle arrest, regulation of cell differentiation, growth factors and cytokine levels, synaptic functions, apoptosis, cell adhesion and cell signaling, and regulation of transcription displayed stable expression in the DG with aging. The exceptions included increased expression of genes important for NSC proliferation and neurogenesis (Stat3 and Shh), DNA damage response and NFkappaB signaling (Cdk5rap3), neuromodulation (Adora1), and decreased expression of a gene important for neuronal differentiation (HeyL). Thus, age-related decrease in hippocampal neurogenesis is not associated with a decline in the expression of selected genes important for NSC proliferation and neurogenesis in the DG.

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Is there a link between adult neurogenesis and learning?

Cited by 477 publications

References 100 publications

Macrophage migration inhibitory factor is critically involved in basal and fluoxetine-stimulated adult hippocampal cell proliferation and in anxiety, depression, and memory-related behaviors

Macrophage migration inhibitory factor is critically involved in basal and fluoxetine-stimulated adult hippocampal cell proliferation and in anxiety, depression, and memory-related behaviors

Diabetes impairs hippocampal function through glucocorticoid-mediated effects on new and mature neurons

Neural stem cell- and neurogenesis-related gene expression profiles in the young and aged dentate gyrus

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