Hippocampus-dependent learning promotes survival of new neurons in the dentate gyrus at a specific time during cell maturation

Epp, Jonathan R.; Spritzer, Mark D.; Galea, Liisa A.M.

doi:10.1016/j.neuroscience.2007.07.046

Cited by 162 publications

(164 citation statements)

References 48 publications

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“…As previously reported in rats, our results indicate that spatial learning also promoted long-term survival of newborn neurons in the DG of mice (12)(13)(14)24). At the time of remote memory retrieval, assessed by a probe test given 30 days after acquisition, we found that a small but significant number of new neurons were activated, thereby revealing their functional contribution to relevant hippocampal assemblies that enable spatial navigation to the hidden goal.…”

Section: Discussionsupporting

confidence: 87%

“…1B and Table S1]. This finding is in agreement with previous reports indicating that both locomotor activity and learning associated with water maze training enhance short-term survival of 9-day-old hippocampal cells (12)(13)(14). In contrast, the survival rate of 39-day-old hippocampal cells was increased in Spatial ϪPF (56%) compared with Cage and Swim controls (26% and 35%, respectively; Fig.…”

Section: Spatial Learning Promotes Survival Of Adult-generated Hippocsupporting

confidence: 91%

“…As shown in Fig. 2, Zif268 expression in the DG was higher in Spatial ϪPF animals compared with Cage and Swim controls [F (2,14) ϭ 17.55; P Ͻ 0.001]. These findings support an involvement of the hippocampus in the expression of remote spatial memory assessed in behavioral paradigms that require animals to navigate through space (17).…”

Section: Retrieval Of Remote Spatial Memory Engages Hippocampal-corticalsupporting

confidence: 65%

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Recruitment of adult-generated neurons into functional hippocampal networks contributes to updating and strengthening of spatial memory

Trouche

Bontempi

Roullet

et al. 2009

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

170

135

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The dentate gyrus (DG), a hippocampal subregion, continuously produces new neurons in the adult mammalian brain that become functionally integrated into existing neural circuits. To what extent this form of plasticity contributes to memory functions remains to be elucidated. Using mapping of activity-dependent gene expression, we visualized in mice injected with the birthdating marker 5-bromo-2 -deoxyuridine the recruitment of new neurons in a set of controlled water maze procedures that engage specific spatial memory processes and require hippocampal-cortical networks. Here, we provide new evidence that adult-generated hippocampal neurons make a specific but differential contribution to the processing of remote spatial memories. First, we show that new neurons in the DG are recruited into neuronal networks that support retrieval of remote spatial memory and that their activation is situation-specific. We further reveal that once selected, new hippocampal neurons are durably incorporated into memory circuits, and also that their recruitment into hippocampal networks contributes predominantly to the updating and strengthening of a previously encoded memory. We find that initial spatial training during a critical period, when new neurons are more receptive to surrounding neuronal activity, favors their subsequent recruitment upon remote memory retrieval. We therefore hypothesize that new neurons activated during this critical period become tagged so that once mature, they are preferentially recruited into hippocampal networks underlying remote spatial memory representation when encountering a similar experience.immediate early gene ͉ learning ͉ memory consolidation ͉ neurogenesis ͉ plasticity N ew neurons are generated throughout adult life in discrete regions of the mammalian brain, including the dentate gyrus (DG) of the hippocampus. Some of these newborn neurons become integrated into preexisting hippocampal circuits, raising the possibility that they may thereby contribute to behaviorally relevant neuronal assemblies. Supporting this idea, the increasing number of reports that have used correlative and invasive approaches indicates the existence of a functional link between hippocampal-dependent learning and adult hippocampal neurogenesis (1-5). Recently, it was found that new cells contribute to the functional activity patterns elicited in the hippocampus in response to performing memory tasks that solicit hippocampal networks (4, 6, 7).To date, the nature of the specific contributions of adultgenerated neurons to memory processing remains largely unknown. During the second week after birth, new hippocampal cells enter a period during which they show enhanced synaptic plasticity, their functional maturation occurs, and their ultimate survival is determined (8, 9). At this age, depletion of new neurons leads to memory impairment in several hippocampaldependent tasks (1, 3). Based on these observations, we sought to examine in mice injected with the birthdating marker 5-bromo-2Ј-deoxyuridine (BrdU) the contribu...

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Section: Discussionsupporting

confidence: 87%

Section: Spatial Learning Promotes Survival Of Adult-generated Hippocsupporting

confidence: 91%

Section: Retrieval Of Remote Spatial Memory Engages Hippocampal-corticalsupporting

confidence: 65%

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Recruitment of adult-generated neurons into functional hippocampal networks contributes to updating and strengthening of spatial memory

Trouche

Bontempi

Roullet

et al. 2009

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

170

135

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“…One-week treatment of rats with dimebon at a dose of 0.1 mkM/kg (0.32 mg/kg) increased the number of BrdU-positive cells in the dentate gyrus. Because activation of structural plasticity and neurogenesis in the hippocampus is well demonstrated to be implicated in the mechanisms of contextual and spatial learning (Epp et al, 2007;Yang et al, 2008;Li et al, 2010;Pieper et al, 2010), we suggest that this effect might be one of the potential mechanisms which underlie the memory enhancing action of dimebon observed in the current study. Further experiments are required to address the possible link between the mnemonic effects of dimebon and its properties as a proneurogenic compound.…”

Section: Discussionmentioning

confidence: 59%

Dimebon enhances hippocampus-dependent learning in both appetitive and inhibitory memory tasks in mice

Vignisse

Steinbusch

Bolkunov

et al. 2011

Progress in Neuro-Psychopharmacology and Biological Psychiatry

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a b s t r a c t a r t i c l e i n f oPre-clinical and clinical studies on dimebon (dimebolin or latrepirdine) have demonstrated its use as a cognitive enhancer. Here, we show that dimebon administered to 3-month-old C57BL6N mice 15 min prior to training in both appetitive and inhibitory learning tasks via repeated (0.1 mg/kg) and acute (0.5 mg/kg) i.p. injections, respectively, increases memory scores. Acute treatment with dimebon was found to enhance inhibitory learning, as also shown in the step-down avoidance paradigm in 7-month-old mice. Bolus administration of dimebon did not affect the animals' locomotion, exploration or anxiety-like behaviour, with the exception of exploratory behaviour in older mice in the novel cage test. In a model of appetitive learning, a spatial version of the Y-maze, dimebon increased the rate of correct choices and decreased the latency of accessing a water reward after water deprivation, and increased the duration of drinking behaviour during training/testing procedures. Repeated treatment with dimebon did not alter the behaviours in other tests or water consumption. Acute treatment of water-deprived and non-water-deprived mice with dimebon also did not affect their water intake. Our data suggest that dimebon enhances hippocampus-dependent learning in both appetitive and inhibitory tasks in mice.

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“…Adult neurogenesis in the rat hippocampus is affected by learning and is perhaps involved in related processes (3)(4)(5)(6)(7). Specifically, it has been shown that learning a new task enhances the survival of the new cells that were generated in the dentate gyrus (DG) of the hippocampus 1 week before the training began (8)(9)(10)(11)(12)(13), while it has no effect on other neurogenic regions, such as the subventricular zone (11). The vast majority of these surviving cells differentiate into neurons and many are incorporated into the circuitry of the hippocampus (7,12,14,15).…”

mentioning

confidence: 99%

Female rats learn trace memories better than male rats and consequently retain a greater proportion of new neurons in their hippocampi

Dalla

Papachristos

Whetstone

et al. 2009

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

108

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Learning increases the survival of new cells that are generated in the hippocampal formation before the training experience, especially if the animal learns to associate stimuli across time [Gould E, Beylin A, Tanapat P, Reeves A, Shors TJ (1999) Nat Neurosci 2:260 -265]. All relevant studies have been conducted on male rats, despite evidence for sex differences in this type of learning. In the present study, we asked whether sex differences in learning influence the survival of neurons generated in the adult hippocampus. Male and female adult rats were injected with one dose of bromodeoxyuridine (BrdU; 200 mg/kg), to label one population of dividing cells. One week later, half of the animals were trained with a temporal learning task of trace eyeblink conditioning, while the other half were not trained. Animals were killed 1 day after training (12 days after the BrdU injection). Hippocampal tissue was stained for BrdU and a marker of immature neurons, doublecortin. Both sexes learned to emit the conditioned eyeblink response during the trace interval. As a consequence, more new neurons remained in their hippocampi than in sex-matched controls. In individual animals, the number of surviving cells correlated positively with asymptotic performance; those that expressed more learned responses retained more new neurons. However, animals that learned very well retained even more new cells if they required many trials to do so. Because females emitted more learned responses than males did, they retained nearly twice as many new cells per unit volume of tissue. This effect was most evident in the ventral region of the hippocampal formation. Thus, sex differences in learning alter the anatomical structure of the hippocampus. As a result, male and female brains continue to differentiate in adulthood.eyeblink conditioning ͉ learning ͉ neurogenesis ͉ sex differences ͉ stem cell

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Hippocampus-dependent learning promotes survival of new neurons in the dentate gyrus at a specific time during cell maturation

Cited by 162 publications

References 48 publications

Recruitment of adult-generated neurons into functional hippocampal networks contributes to updating and strengthening of spatial memory

Recruitment of adult-generated neurons into functional hippocampal networks contributes to updating and strengthening of spatial memory

Dimebon enhances hippocampus-dependent learning in both appetitive and inhibitory memory tasks in mice

Female rats learn trace memories better than male rats and consequently retain a greater proportion of new neurons in their hippocampi

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