Adult neurogenesis in the mammalian hippocampus: Why the dentate gyrus?

Drew, Liam; Fusi, Stefano; Hen, René

doi:10.1101/lm.026542.112

Cited by 125 publications

(121 citation statements)

References 242 publications

(381 reference statements)

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“…This is noteworthy because the dentate gyrus is one of two sites in the adult central nervous system (CNS) where neurogenesis occurs (Drew et al 2013). In vitro studies indicate that Wnt/β-catenin signaling is necessary and sufficient for adult hippocampal neurogenesis (Lie et al 2005).…”

Section: Discussionmentioning

confidence: 99%

Neuroanatomical Distribution of DEK Protein in Corticolimbic Circuits Associated with Learning and Memory in Adult Male and Female Mice

et al. 2018

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DEK, a chromatin-remodeling gene expressed in most human tissues, is known for its role in cancer biology and autoimmune diseases. DEK depletion in vitro reduces cellular proliferation, induces DNA damage subsequently leading to apoptosis, and down-regulates canonical Wnt/β-catenin signaling, a molecular pathway essential for learning and memory. Despite a recognized role in cancer (non-neuronal) cells, DEK expression and function is not well characterized in the central nervous system. We conducted a gene ontology analysis (ToppGene), using a cancer database to identify genes associated with DEK deficiency, which pinpointed several genes associated with cognitive-related diseases (i.e., Alzheimer’s disease, presenile dementia). Based on this information, we examined DEK expression in corticolimbic structures associated with learning and memory in adult male and female mice using immunohistochemistry. DEK was expressed throughout the brain in both sexes, including the medial prefrontal cortex (prelimbic, infralimbic and dorsal peduncular). DEK was also abundant in all amygdalar subdivisions (basolateral, central and medial) and in the hippocampus including the CA1, CA2, CA3, dentate gyrus (DG), ventral subiculum and entorhinal cortex. Of note, compared to males, females had significantly higher DEK immunoreactivity in the CA1, indicating a sex difference in this region. DEK was co-expressed with neuronal and microglial markers in the CA1 and DG, whereas only a small percentage of DEK cells were in apposition to astrocytes in these areas. Given the reported inverse cellular and molecular profiles (e.g., cell survival, Wnt pathway) between cancer and Alzheimer’s disease, these findings suggest a potentially important role of DEK in cognition.

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Section: Discussionmentioning

confidence: 99%

Neuroanatomical Distribution of DEK Protein in Corticolimbic Circuits Associated with Learning and Memory in Adult Male and Female Mice

et al. 2018

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“…These observations beg the question how adult-born DGCs influence global remapping in the DG and CA3(Piatti et al, 2013).We recently proposed a role for adult-born DGCs in recruiting feed-back inhibition to modulate sparseness of coding to support pattern separation in the DG(Sahay et al, 2011a;Drew et al, 2013). According to this model, increasing the number of adult-born DGCs would enhance sparseness of activity in the DG and consequently, promote global remapping.…”

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confidence: 95%

Adult Hippocampal Neurogenesis, Fear Generalization, and Stress

Besnard

Sahay

2015

Neuropsychopharmacol

182

159

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The generalization of fear is an adaptive, behavioral, and physiological response to the likelihood of threat in the environment. In contrast, the overgeneralization of fear, a cardinal feature of posttraumatic stress disorder (PTSD), manifests as inappropriate, uncontrollable expression of fear in neutral and safe environments. Overgeneralization of fear stems from impaired discrimination of safe from aversive environments or discernment of unlikely threats from those that are highly probable. In addition, the time-dependent erosion of episodic details of traumatic memories might contribute to their generalization. Understanding the neural mechanisms underlying the overgeneralization of fear will guide development of novel therapeutic strategies to combat PTSD. Here, we conceptualize generalization of fear in terms of resolution of interference between similar memories. We propose a role for a fundamental encoding mechanism, pattern separation, in the dentate gyrus (DG)-CA3 circuit in resolving interference between ambiguous or uncertain threats and in preserving episodic content of remote aversive memories in hippocampal-cortical networks. We invoke cellular-, circuit-, and systems-based mechanisms by which adult-born dentate granule cells (DGCs) modulate pattern separation to influence resolution of interference and maintain precision of remote aversive memories. We discuss evidence for how these mechanisms are affected by stress, a risk factor for PTSD, to increase memory interference and decrease precision. Using this scaffold we ideate strategies to curb overgeneralization of fear in PTSD.

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“…For instance, we do not understand adaptive reasons for the wide variations among taxonomic groups in numbers and types of new neurons that continue to be produced throughout life, or variations in the brain regions that receive new neurons. Perhaps one of the most intriguing puzzles is why both numbers and types of constitutive new neurons produced in adulthood appear to be most restricted in mammals [Gould, 2007;Drew et al, 2013], although much needed comparative approaches may reveal more species differences within mammals than has been previously assumed [Bonfanti and Peretto, 2011]. In addition, some brain regions seem to replace existing neurons with new ones [Scharff et al, 2000;Barnea et al, 2006;Quadrato et al, 2014], while evidence suggests that other regions continually pack in additional neurons in the absence of compensatory cell death [Walton et al, 2012].…”

Section: Introductionmentioning

confidence: 99%

Adult Neurogenesis in the Songbird: Region-Specific Contributions of New Neurons to Behavioral Plasticity and Stability

Pytte

2016

Brain Behav Evol

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Our understanding of the role of new neurons in learning and encoding new information has been largely based on studies of new neurons in the mammalian dentate gyrus and olfactory bulb - brain regions that may be specialized for learning. Thus the role of new neurons in regions that serve other functions has yet to be fully explored. The song system provides a model for studying new neuron function in brain regions that contribute differently to song learning, song auditory discrimination, and song motor production. These regions subserve learning as well as long-term storage of previously learned information. This review examines the differences between learning-based and activity-based retention of new neurons and explores the potential contributions of new neurons to behavioral stability in the song motor production pathway.

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Adult neurogenesis in the mammalian hippocampus: Why the dentate gyrus?

Cited by 125 publications

References 242 publications

Neuroanatomical Distribution of DEK Protein in Corticolimbic Circuits Associated with Learning and Memory in Adult Male and Female Mice

Neuroanatomical Distribution of DEK Protein in Corticolimbic Circuits Associated with Learning and Memory in Adult Male and Female Mice

Adult Hippocampal Neurogenesis, Fear Generalization, and Stress

Adult Neurogenesis in the Songbird: Region-Specific Contributions of New Neurons to Behavioral Plasticity and Stability

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