Maturation and Functional Integration of New Granule Cells into the Adult Hippocampus

Toni, Nicolas; Schinder, Alejandro F.

doi:10.1101/cshperspect.a018903

Cited by 151 publications

(129 citation statements)

References 85 publications

(119 reference statements)

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“…These young adult-born neurons in their critical period of development have distinct electrophysiological properties, including high input resistance and a lack of GABAergic inhibition, which results in these cells having a greater propensity for hyperexcitability and exhibiting lower activation thresholds than mature granule cells. Young adult-born neurons also show enhanced plasticity and long-term potentiation, which are mediated by NR2B-containing NMDA receptors 36,39,40 . In addition, 4–6-week-old neurons make a unique contribution to hippocampus-dependent behaviours 41 .…”

Section: Dentate Gyrus Functionmentioning

confidence: 99%

“…At the microcircuit level, presynaptic terminals onto hilar interneurons develop at ~4 weeks of age and recruit feedback inhibition onto mature granule neurons 40,54 (see the figure, part a ). Accordingly, increasing neurogenesis in mice through environmental enrichment or transgenic strategies inhibits mature granule cells and reduces the overall excitability of the DG 68,69 .…”

Section: Figure 1 |mentioning

confidence: 99%

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Adult hippocampal neurogenesis and cognitive flexibility — linking memory and mood

2017

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Adult hippocampal neurogenesis has been implicated in cognitive processes, such as pattern separation, and in the behavioural effects of stress and antidepressants. Young adult-born neurons have been shown to inhibit the overall activity of the dentate gyrus by recruiting local interneurons, which may result in sparse contextual representations and improved pattern separation. We propose that neurogenesis-mediated inhibition also reduces memory interference and enables reversal learning both in neutral situations and in emotionally charged ones. Such improved cognitive flexibility may in turn help to decrease anxiety-like and depressive-like behaviour.

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Section: Dentate Gyrus Functionmentioning

confidence: 99%

Section: Figure 1 |mentioning

confidence: 99%

Adult hippocampal neurogenesis and cognitive flexibility — linking memory and mood

2017

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“…The cells progress from a state with high input resistance to the normal membrane properties of mature granule cells. (For more details on the functional maturation of the new neurons, please refer to Schinder 2015 andSong et al 2015. )…”

Section: Adult Hippocampal Neurogenesismentioning

confidence: 99%

Neurogenesis in the Adult Hippocampus

Kempermann

Song²,

Gage

2015

Cold Spring Harb Perspect Biol

780

609

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Of the neurogenic zones in the adult brain, adult hippocampal neurogenesis attracts the most attention, because it is involved in higher cognitive function, most notably memory processes, and certain affective behaviors. Adult hippocampal neurogenesis is also found in humans at a considerable level and appears to contribute significantly to hippocampal plasticity across the life span, because it is regulated by activity. Adult hippocampal neurogenesis generates new excitatory granule cells in the dentate gyrus, whose axons form the mossy fiber tract that links the dentate gyrus to CA3. It originates from a population of radial glia-like precursor cells (type 1 cells) that have astrocytic properties, express markers of neural stem cells and divide rarely. They give rise to intermediate progenitor cells with first glial (type 2a) and then neuronal (type 2b) phenotype. Through a migratory neuroblast-like stage (type 3), the newborn, lineage-committed cells exit the cell cycle and enter a maturation stage, during which they extend their dendrites into a the molecular layer and their axon to CA3. They go through a period of several weeks, during which they show increased synaptic plasticity, before finally becoming indistinguishable from the older granule cells.

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“…The observation that adult neurogenesis is regulated by activity cannot be considered independent of a functional theory (see Toni and Schinder 2015 for detailed discussion). If "activity" means "functionally relevant activity" (which remains to be proven) the regulation becomes part of the function because learning and structural change are tightly and causally linked.…”

mentioning

confidence: 99%

Activity Dependency and Aging in the Regulation of Adult Neurogenesis

Kempermann

2015

Cold Spring Harb Perspect Biol

100

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Age and activity might be considered the two antagonistic key regulators of adult neurogenesis. Adult neurogenesis decreases with age but remains present, albeit at a very low level, even in the oldest individuals. Activity, be it physical or cognitive, increases adult neurogenesis and thereby seems to counteract age effects. It is, thus, proposed that activity-dependent regulation of adult neurogenesis might contribute to some sort of "neural reserve," the brain's ability to compensate functional loss associated with aging or neurodegeneration. Activity can have nonspecific and specific effects on adult neurogenesis. Mechanistically, nonspecific stimuli that largely affect precursor cell stages might be related by the local microenvironment, whereas more specific, survival-promoting effects take place at later stages of neuronal development and require the synaptic integration of the new cell and its particular synaptic plasticity.

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Maturation and Functional Integration of New Granule Cells into the Adult Hippocampus

Cited by 151 publications

References 85 publications

Adult hippocampal neurogenesis and cognitive flexibility — linking memory and mood

Adult hippocampal neurogenesis and cognitive flexibility — linking memory and mood

Neurogenesis in the Adult Hippocampus

Activity Dependency and Aging in the Regulation of Adult Neurogenesis

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