Enhanced synaptic plasticity in newly generated granule cells of the adult hippocampus

Schmidt-Hieber, Christoph; Jónás, Péter; Bischofberger, Josef

doi:10.1038/nature02553

Cited by 1,158 publications

(923 citation statements)

References 30 publications

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“…3B). These results support previous reports that young neurons in the DG exhibit a lack of GABAergic inhibition and are, therefore, more receptive to the induction of LTP (28)(29)(30)(31).…”

Section: Fear Conditioning In Glial Fibrillary Acidic Protein (Gfap)-supporting

confidence: 82%

“…Single-cell recordings have demonstrated that young neurons are more excitable than mature granule cells because of properties such as an elevated resting membrane potential, high input resistance, and low-threshold calcium channel expression (29,31). In addition, young neurons (2-4 wk old) are not inhibited, and can in fact be depolarized, by GABAergic activity (30,32).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

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

Saxe¹,

Battaglia²,

Wang³

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

924

839

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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.long-term potentiation ͉ learning ͉ memory N ew neurons are born in the dentate gyrus (DG) of the hippocampus throughout the life of mammals (1) and derive from dividing progenitor cells located in the innermost part of the granule cell layer, a region called the subgranular zone. Young granule neurons integrate into the existing circuitry of the hippocampus, as evidenced by the development of functional synaptic inputs provided by the medial perforant path (MPP) and growth of axons to target cells in CA3 (2). Although a variety of environmental and pharmacological manipulations can affect neurogenesis (2, 3), it is unclear whether adult-born neurons provide a significant contribution to hippocampal function and, ultimately, how it might impact behavior.Recent studies have shown that various strategies to disrupt neurogenesis produce a limited impairment in some hippocampaldependent learning and memory tasks and in responses to antidepressant drugs (4-11). Unfortunately, the lack of spatial and cellular specificity provided by most ablation techniques has made it difficult to ascertain whether the consequent behavioral effects were caused by ablation of neurogenesis or other impairments. To circumvent these problems we have used two independent strategies of ablation. The first is a previously reported x-ray procedure that differs from similar methods in two ways: (i) the x-ray administration is restricted to a fraction of the brain containing the hippocampus and spares neurogenesis in the neighboring subventricular zone; and (ii) mice are allowed to recover for 3 months before testing to allow for the disappearance of markers of inflammation, such as reactive microglia (9). The second method of ablation is a genetic strategy that directly targets dividing progenitors throughout the brain and avoids potential radi...

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Section: Fear Conditioning In Glial Fibrillary Acidic Protein (Gfap)-supporting

confidence: 82%

Section: Discussionmentioning

confidence: 99%

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

Saxe¹,

Battaglia²,

Wang³

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

924

839

View full text Add to dashboard Cite

show abstract

“…However, our data strongly supports the hypothesis that new neurons need to compete for synaptic partners to ensure proper integration and survival [22]. Interestingly, it has been shown that during the first 3-6 weeks after their birth, new granule cells are highly excitable and show a higher degree of plasticity compared to mature granule cells [17] [18] [19] [21]. This unique feature has been attributed to their special functional properties with emerging evidence supporting the idea that adult neurogenesis in the DG is not a process for mere cell replacement but that new neurons exert their function at least partially due to these special properties [37] [38] [39].…”

Section: Resultssupporting

confidence: 72%

“…During the phase of integration, newborn granule cells are highly excitable and remain so for approximately 6 weeks. This period of high cellular plasticity has been associated with unique functional properties of new neurons and may help new neurons to successfully integrate into the pre-existing circuit [17] [18] [19] [20] [21]. Indeed, it has been suggested that new neurons compete for synaptic partners allowing for stable integration and subsequent survival [22].…”

Section: Introductionmentioning

confidence: 99%

Enhanced plasticity of mature granule cells reduces survival of newborn neurons in the adult mouse hippocampus

et al. 2016

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Dentate granule cells are born throughout life in the mammalian hippocampus. The integration of newborn neurons into the dentate circuit is activity-dependent, and structural data characterizing synapse formation suggested that the survival of adult-born granule cells is regulated by competition for synaptic partners. Here we tested this hypothesis by using a mouse model with genetically enhanced plasticity of mature granule cells through temporally controlled expression of a nuclear inhibitor of protein phosphatase 1 (NIPP 1 *). Using thymidine analogues and retrovirus-mediated cell labeling, we show that synaptic integration and subsequent survival of newborn neurons is decreased in NIPP 1 *-expressing mice, suggesting that newborn neurons compete with preexisting granule cells for stable integration. The data presented here provides experimental evidence for a long-standing hypothesis and suggest cellular competition as a key mechanism regulating the integration and survival of newborn granule cells in the adult mammalian hippocampus.

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“…The formation of newly-generated neurons in the hippocampus is associated with learn and memory abilities (Song et al, 2002;Schmidt-Hieber et al, 2004). When subjected to DHA chronically, both the young and aged rats' learning ability is improved (Gamoh et al, 1999;.…”

Section: Discussionmentioning

confidence: 99%

The Anti-brain Ageing Effects of Krill Phosphatidylserine in SAMP10 Mice

Wang¹,

Lei²,

Li³

et al. 2012

JAS

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We examined the biological effect of krill phosphatidylserine (K-PS) on brain ageing and investigated the mechanisms that how K-PS works on the brain using senescence-accelerated mouse (SAM) model with age-associated neurodegeneration. SAMP10 mice with 5 months of age were treated orally once a day for 75 days with 10 or 100 mg kg −1 d −1 K-PS (low and high dose). The effect of K-PS treatment on the cross-sectional area and Nissl body number of the neocortex at point C, an area prone to atrophy in SAMP10 mice, behavior and oxidative stress were evaluated by Image-Pro Plus software, step-down testing, and malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) assays. Ionized calcium binding adaptor molecule 1 (Iba-1) and insulin-like growth factor 1 (IGF-1) expression was evaluated using immunohistochemistry. Low or high doses of K-PS significantly increased the cross-sectional area and Nissl body number at point C, partly reversed memory impairment, increased the activity of GSH-Px and reduced MDA levels. Moreover, immunohistochemistry indicated that K-PS suppressed Iba-1 expression and upregulate the expression of IGF-1. These findings suggest that K-PS could prevent or slow the progression of brain atrophy and neuronal damage associated with aging by the inhibition of Iba-1 and the upregulation of IGF-1 expression.

show abstract

Enhanced synaptic plasticity in newly generated granule cells of the adult hippocampus

Cited by 1,158 publications

References 30 publications

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

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

Enhanced plasticity of mature granule cells reduces survival of newborn neurons in the adult mouse hippocampus

The Anti-brain Ageing Effects of Krill Phosphatidylserine in SAMP10 Mice

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