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Ablation of hippocampal neurogenesis impairs contextual fear conditioning and synaptic plasticity in the dentate gyrus

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TLDR
The findings show that adult-born neurons make a distinct contribution to some but not all hippocampal functions and show that new hippocampal neurons can be preferentially recruited over mature granule cells in vitro and may provide a framework for how this small cell population can influence behavior.
Abstract
Although hippocampal neurogenesis has been described in many adult mammals, the functional impact of this process on physiology and behavior remains unclear. In the present study, we used two independent methods to ablate hippocampal neurogenesis and found that each procedure caused a limited behavioral deficit and a loss of synaptic plasticity within the dentate gyrus. Specifically, focal X irradiation of the hippocampus or genetic ablation of glial fibrillary acidic protein-positive neural progenitor cells impaired contextual fear conditioning but not cued conditioning. Hippocampal-dependent spatial learning tasks such as the Morris water maze and Y maze were unaffected. These findings show that adult-born neurons make a distinct contribution to some but not all hippocampal functions. In a parallel set of experiments, we show that long-term potentiation elicited in the dentate gyrus in the absence of GABA blockers requires the presence of new neurons, as it is eliminated by each of our ablation procedures. These data show that new hippocampal neurons can be preferentially recruited over mature granule cells in vitro and may provide a framework for how this small cell population can influence behavior.

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Journal ArticleDOI

Mechanisms and functional implications of adult neurogenesis.

TL;DR: The factors that regulate proliferation and fate determination of adult neural stem cells are discussed and the potential significance of adult neurogenesis in memory, depression, and neurodegenerative disorders such as Alzheimer's and Parkinson's disease is addressed.
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New neurons and new memories: how does adult hippocampal neurogenesis affect learning and memory?

TL;DR: Recent progress in the integration of adult-born neurons into the circuitry of the adult hippocampus suggests an important role for adult hippocampal neurogenesis in learning and memory, but its specific function in these processes has remained elusive.
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Stress, Depression, and Neuroplasticity: A Convergence of Mechanisms

TL;DR: Greater appreciation of the convergence of mechanisms between stress, depression, and neuroplasticity is likely to lead to the identification of novel targets for more efficacious treatments.
Journal ArticleDOI

Increasing adult hippocampal neurogenesis is sufficient to improve pattern separation.

TL;DR: It is shown that inducible genetic expansion of the population of adult-born neurons through enhancing their survival improves performance in a specific cognitive task in which two similar contexts need to be distinguished, which is indicative of enhanced pattern separation.
References
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Journal ArticleDOI

Validation of open:closed arm entries in an elevated plus-maze as a measure of anxiety in the rat.

TL;DR: A novel test for the selective identification of anxiolytic and anxiogenic drug effects in the rat is described, using an elevated + -maze consisting of two open arms and two enclosed arms, which showed that behaviour on the maze was not clearly correlated either with exploratory head-dipping or spontaneous locomotor activity.
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Requirement of Hippocampal Neurogenesis for the Behavioral Effects of Antidepressants

TL;DR: It is shown that disrupting antidepressant-induced neurogenesis blocks behavioral responses to antidepressants, suggesting that the behavioral effects of chronic antidepressants may be mediated by the stimulation of neuroGenesis in the hippocampus.
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Differential Contribution of Amygdala and Hippocampus to Cued and Contextual Fear Conditioning

TL;DR: An associative roles for the amygdala and a sensory relay role for the hippocampus are suggested in fear conditioning, which is involved in the conditioning of fear responses to simple, modality-specific conditioned stimuli as well as to complex, polymodal stimuli.
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Functional neurogenesis in the adult hippocampus

TL;DR: It is reported that newly generated cells in the adult mouse hippocampus have neuronal morphology and can display passive membrane properties, action potentials and functional synaptic inputs similar to those found in mature dentate granule cells.
Journal ArticleDOI

Neurogenesis in the adult is involved in the formation of trace memories

TL;DR: It is shown that a substantial reduction in the number of newly generated neurons in the adult rat impairs hippocampal-dependent trace conditioning, a task in which an animal must associate stimuli that are separated in time.
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