Aimone JB, Wiles J, Gage FH. Potential role for adult neurogenesis in the encoding of time in new memories. Nat Neurosci 9: 723-727

Laboratory of Genetics, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037, USA.
Nature Neuroscience (Impact Factor: 16.1). 07/2006; 9(6):723-7. DOI: 10.1038/nn1707
Source: PubMed


The dentate gyrus in the hippocampus is one of two brain regions with lifelong neurogenesis in mammals. Despite an increasing amount of information about the characteristics of the newborn granule cells, the specific contribution of their robust generation to memory formation by the hippocampus remains unclear. We describe here a possible role that this population of young granule cells may have in the formation of temporal associations in memory. Neurogenesis is a continuous process; the newborn population is only composed of the same cells for a short period of time. As time passes, the young neurons mature or die and others are born, gradually changing the identity of this young population. We discuss the possibility that one cognitive impact of this gradually changing population on hippocampal memory formation is the formation of the temporal clusters of long-term episodic memories seen in some human psychological studies.

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    • "When similar items are spaced closely in time, some models predict that neurogenesis should increase 49 pattern integration (Aimone et al., 2006, 2009). By the same token, the reverse should be true of 50 animals with reduced neurogenesis: they should exhibit impaired pattern integration, and therefore, "
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    ABSTRACT: The hippocampus has been the focus of memory research for decades. While the functional role of this structure is not fully understood, it is widely recognized as being vital for rapid yet accurate encoding of associative memories. Since the discovery of adult hippocampal neurogenesis in the dentate gyrus by Altman and Das in the 1960's, many theories and models have been put forward to explain the functional role it plays in learning and memory. These models postulate different ways in which new neurons are introduced into the dentate gyrus and their functional importance for learning and memory. Few if any previous models have incorporated the full range of unique physiological properties of young adult-born dentate granule cells and their developmental trajectory. In this paper, we propose a novel computational model of the dentate gyrus that incorporates the developmental trajectory of adult-born dentate granule cells, including changes in synaptic plasticity, connectivity, excitability and lateral inhibition, using a modified version of the Restricted Boltzmann Machine. Our results show superior performance on memory reconstruction tasks for both recent and distally learned items, when the unique characteristics of young dentate granule cells are taken into account. Even though the hyperexcitability of the young neurons generates more overlapping neural codes, reducing pattern separation, the unique properties of the young neurons nonetheless contribute to reducing retroactive and proactive interference, at both short and long time scales. The sparse connectivity is particularly important for generating distinct memory traces for highly overlapping patterns that are learned within the same context.
    Frontiers in Systems Neuroscience 10/2015; DOI:10.3389/fnsys.2015.00136
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    • "The current results, however, show that noxious stimuli delivered on P1 or P8 did not increase the ability of male animals to recognize a new, unknown object as compared to control to non-stimulated controls. Previous findings have shown that adult neurogenesis may be involved in specific aspects of hippocampal function, such as the acquisition of new information (Kempermann & Cage, 2002) and the encoding of temporal cues (Aimone et al., 2006). We did not observed any differences in the retention of new knowledge. "
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    ABSTRACT: Prematurely-born infants are exposed to multiple invasive procedures while in the intensive care unit. Newborn rats and humans have similar behavioral responses to noxious stimulation. Previous studies have shown that early noxious stimuli may alter dentate gyrus neurogenesis and the behavioral repertoire of adult rats. We evaluated the late effects of noxious stimulation administered during different phases of development on two spatial memory tests; object recognition (OR) and Morris water maze (WM) tests. Noxious stimulation was induced by an intra-plantar injection of Complete Freund's adjuvant (CFA) on postnatal (P) day 1 (group P1) or 8 (P8). Control animals were not stimulated. Behavioral tests were conducted on P60 in both male and female animals. In the WM, three domains were evaluated: acquisition, probe trial performance and reversal re-acquisition. The number of Nissl stained cells in the dentate granule cell layer was assessed by stereological counting. The OR test revealed that P1 male rats had poor long-term memory compared to the control and P8 groups. In the WM, no short- or long-term memory differences were detected between early postnatal-stimulated male and female rats and their respective controls. However, the ability to find the hidden platform in a new position was reduced in P1 male rats. The number of dentate granule cells in P8 males was higher than in all other groups. This study demonstrates that noxious stimulation on P1 results in spatial learning deficits in male animals, but does not disrupt the development of the hippocampus-dependent strategies of learning and memory.
    Neurobiology of Learning and Memory 09/2015; 125. DOI:10.1016/j.nlm.2015.08.012 · 3.65 Impact Factor
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    • "In adult neurogenesis, the newly generated neurons integrate multiple signals, form new synapses in the hippocampus (Aimone et al. 2006; van Praag et al. 2002) and are thought to have an important role in learning and memory and in adaptive responses in neurodegenerative disorders (Lazarov et al. 2010). In agreement with these findings, compounds that positively influence neurogenesis are associated with enhanced performance in hippocampal-dependent learning tasks (Ahn et al. 2014; Lee et al. 2013a; Snyder et al. 2005). "
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    ABSTRACT: Exposure to organophosphorous (OP) nerve agents such as soman inhibits the critical enzyme acetylcholinesterase (AChE) leading to excessive acetylcholine accumulation in synapses, resulting in cholinergic crisis, status epilepticus and brain damage in survivors. The hippocampus is profoundly damaged after soman exposure leading to long-term memory deficits. We have previously shown that treatment with three sequential doses of alpha-linolenic acid, an essential omega-3 polyunsaturated fatty acid, increases brain plasticity in naïve animals. However, the effects of this dosing schedule administered after a brain insult and the underlying molecular mechanisms in the hippocampus are unknown. We now show that injection of three sequential doses of alpha-linolenic acid after soman exposure increases the endogenous expression of mature BDNF, activates Akt and the mammalian target of rapamycin complex 1 (mTORC1), increases neurogenesis in the subgranular zone of the dentate gyrus, increases retention latency in the passive avoidance task and increases animal survival. In sharp contrast, while soman exposure also increases mature BDNF, this increase did not activate downstream signaling pathways or neurogenesis. Administration of the inhibitor of mTORC1, rapamycin, blocked the alpha-linolenic acid-induced neurogenesis and the enhanced retention latency but did not affect animal survival. Our results suggest that alpha-linolenic acid induces a long-lasting neurorestorative effect that involves activation of mTORC1 possibly via a BDNF-TrkB-mediated mechanism.
    Neuromolecular medicine 04/2015; 17(3). DOI:10.1007/s12017-015-8353-y · 3.68 Impact Factor
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