A Hypothesis About the Role of Adult Neurogenesis in Hippocampal Function

Schinder, Alejandro F.; Gage, Fred H.

doi:10.1152/physiol.00012.2004

Cited by 95 publications

(70 citation statements)

References 54 publications

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“…It is now widely recognized that adult neurogenesis can affect the expression of plasticity in this area (Schinder and Gage, 2004). The present findings that LTP promotes neurogenesis thus add a new prospect to the relationship between Hebbian synaptic plasticity and neurogenesis.…”

Section: Discussionsupporting

confidence: 60%

Long-Term Potentiation Enhances Neurogenesis in the Adult Dentate Gyrus

Bruel-Jungerman¹,

Davis²,

Rampon³

et al. 2006

J. Neurosci.

265

221

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Activity-dependent synaptic plasticity and neurogenesis are two forms of brain plasticity that can participate in functional remodeling of neural networks during the formation of memories. We examined whether long-term potentiation (LTP) of excitatory synaptic transmission, a well characterized form of synaptic plasticity believed to play a critical role in memory formation, can regulate the rate of neurogenesis in the adult rat dentate gyrus in vivo. We first show that induction of LTP at medial perforant path-granule cell synapses stimulates the proliferation of progenitor cells in the dentate gyrus with a consequential long-term persistence of a larger population of surviving newborn cells. Using protocols to examine the effect of LTP on survival, we next show that LTP induction promotes survival of 1-to 2-week-old dentate granule cells. In no case did LTP appear to affect neuronal differentiation. Finally, we show that LTP induces expression of the plasticity-related transcription factor Zif268 in a substantial fraction of 2-week-old but not 1-week-old neurons, suggesting the prosurvival effect of LTP can be observed in the absence of LTP-mediated Zif268 induction in newborn cells. Our results indicate that electrically induced LTP in the dentate gyrus in vivo provides a cellular/molecular environment that favors both proliferation and survival of adult-generated neurons.

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Section: Discussionsupporting

confidence: 60%

Long-Term Potentiation Enhances Neurogenesis in the Adult Dentate Gyrus

Bruel-Jungerman¹,

Davis²,

Rampon³

et al. 2006

J. Neurosci.

265

221

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“…Great efforts are currently being devoted to study the influence of behavior on the rate of adult neurogenesis and the physiological relevance of adult neurogenesis in hippocampal function (van Praag et al, 2000;Shors et al, 2001;Madsen et al, 2003;Santarelli et al, 2003;Schinder and Gage, 2004). In this context, the time course described here for the neuronal maturation (ϳ3-4 weeks) seems extremely slow as a mechanism for plasticity, because it can only modify hippocampal circuits several weeks after neuronal differentiation was initiated.…”

Section: Similarities Between the Developing And Adult Hippocampusmentioning

confidence: 99%

“…Adult hippocampal neurogenesis has been observed in vertebrates from birds to humans (Nottebohm, 2002), yet its physiological significance remains essentially unknown (Schinder and Gage, 2004). However, increasing evidence points to a key role in hippocampal function.…”

Section: Introductionmentioning

confidence: 99%

Neuronal Differentiation in the Adult Hippocampus Recapitulates Embryonic Development

Esposito

Piatti²,

Laplagne³

et al. 2005

J. Neurosci.

593

674

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In the adult hippocampus and olfactory bulb, neural progenitor cells generate neurons that functionally integrate into the existing circuits. To understand how neuronal differentiation occurs in the adult hippocampus, we labeled dividing progenitor cells with a retrovirus expressing green fluorescent protein and studied the morphological and functional properties of their neuronal progeny over the following weeks. During the first week neurons had an irregular shape and immature spikes and were synaptically silent. Slow GABAergic synaptic inputs first appeared during the second week, when neurons exhibited spineless dendrites and migrated into the granule cell layer. In contrast, glutamatergic afferents were detected by the fourth week in neurons displaying mature excitability and morphology. Interestingly, fast GABAergic responses were the latest to appear. It is striking that neuronal maturation in the adult hippocampus follows a precise sequence of connectivity (silent 3 slow GABA 3 glutamate 3 fast GABA) that resembles hippocampal development. We conclude that, unlike what is observed in the olfactory bulb, the hippocampus maintains the same developmental rules for neuronal integration through adulthood.

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“…A number of hypotheses have been developed to explain how new neurons might contribute to hippocampal function (Schinder and Gage 2004;Becker 2005;Aimone et al 2006;Kempermann 2008). Newborn neurons represent only a small cell population within the adult dentate gyrus.…”

Section: Neurogenesis Is Involved In Hippocampal Learningmentioning

confidence: 99%

Dentate gyrus-specific knockdown of adult neurogenesis impairs spatial and object recognition memory in adult rats

Jessberger¹,

Clark²,

Broadbent³

et al. 2009

Learn. Mem.

Self Cite

578

442

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New granule cells are born throughout life in the dentate gyrus of the hippocampal formation. Given the fundamental role of the hippocampus in processes underlying certain forms of learning and memory, it has been speculated that newborn granule cells contribute to cognition. However, previous strategies aiming to causally link newborn neurons with hippocampal function used ablation strategies that were not exclusive to the hippocampus or that were associated with substantial side effects, such as inflammation. We here used a lentiviral approach to specifically block neurogenesis in the dentate gyrus of adult male rats by inhibiting WNT signaling, which is critically involved in the generation of newborn neurons, using a dominant-negative WNT (dnWNT). We found a level-dependent effect of adult neurogenesis on the long-term retention of spatial memory in the water maze task, as rats with substantially reduced levels of newborn neurons showed less preference for the target zone in probe trials >2 wk after acquisition compared with control rats. Furthermore, animals with strongly reduced levels of neurogenesis were impaired in a hippocampus-dependent object recognition task. Social transmission of food preference, a behavioral test that also depends on hippocampal function, was not affected by knockdown of neurogenesis. Here we identified a role for newborn neurons in distinct aspects of hippocampal function that will set the ground to further elucidate, using experimental and computational strategies, the mechanism by which newborn neurons contribute to behavior.

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A Hypothesis About the Role of Adult Neurogenesis in Hippocampal Function

Cited by 95 publications

References 54 publications

Long-Term Potentiation Enhances Neurogenesis in the Adult Dentate Gyrus

Long-Term Potentiation Enhances Neurogenesis in the Adult Dentate Gyrus

Neuronal Differentiation in the Adult Hippocampus Recapitulates Embryonic Development

Dentate gyrus-specific knockdown of adult neurogenesis impairs spatial and object recognition memory in adult rats

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