Young Dentate Granule Cells Mediate Pattern Separation, whereas Old Granule Cells Facilitate Pattern Completion

Nakashiba, Toshiaki; Cushman, Jesse D.; Pelkey, Kenneth A.; Renaudineau, Sophie; Buhl, Derek L.; McHugh, Thomas J.; Barrera, Vanessa Rodriguez; Chittajallu, Ramesh; Iwamoto, Keisuke S.; McBain, Chris J.; Fanselow, Michael S.; Tonegawa, Susumu

doi:10.1016/j.cell.2012.01.046

Cited by 725 publications

(744 citation statements)

References 59 publications

Supporting

Mentioning

702

Contrasting

Order By: Relevance

“…Instead, FXGs are present only after axons become synaptically-integrated into circuits. Further, by manipulating adult neurogenesis, we determined that FXGs persist for months after the period of robust plasticity in newly born adult neurons (30)(31)(32). Therefore, we propose that FXGs regulate local translation in the mature axonal arbour, likely in the context of adult plasticity.…”

Section: Fxgs In the Adult Brainmentioning

confidence: 99%

See 1 more Smart Citation

Axonal ribosomes and mRNAs associate with fragile X granules in adult rodent and human brains

et al. 2017

View full text Add to dashboard Cite

Local mRNA translation in growing axons allows for rapid and precise regulation of protein expression in response to extrinsic stimuli. However, the role of local translation in mature CNS axons is unknown. Such a mechanism requires the presence of translational machinery and associated mRNAs in circuit-integrated brain axons. Here we use a combination of genetic, quantitative imaging and super-resolution microscopy approaches to show that mature axons in the mammalian brain contain ribosomes, the translational regulator FMRP and a subset of FMRP mRNA targets. This axonal translational machinery is associated with Fragile X granules (FXGs), which are restricted to axons in a stereotyped subset of brain circuits. FXGs and associated axonal translational machinery are present in hippocampus in humans as old as 57 years. This FXGassociated axonal translational machinery is present in adult rats, even when adult neurogenesis is blocked. In contrast, in mouse this machinery is only observed in juvenile hippocampal axons. This differential developmental expression was specific to the hippocampus, as both mice and rats exhibit FXGs in mature axons in the adult olfactory system. Experiments in Fmr1 null mice show that FMRP regulates axonal protein expression but is not required for axonal transport of ribosomes or its target mRNAs. Axonal translational machinery is thus a feature of adult CNS neurons. Regulation of this machinery by FMRP could support complex behaviours in humans throughout life.

show abstract

Section: Fxgs In the Adult Brainmentioning

confidence: 99%

“…In the dentate gyrus newly born granule cells are generated throughout life and exhibit a period of heightened plasticity as they integrate into the mature circuitry (30)(31)(32). Adult neurogenesis is more robust in rats than mice (33).…”

Section: The Expression Of Axonal Rna Granules In Adult Hippocampus Imentioning

confidence: 99%

Axonal ribosomes and mRNAs associate with fragile X granules in adult rodent and human brains

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Hippocampal neural activity shows attractor dynamics [51] enabling content-addressable reactivation of the entire stored representation through activation of a particular memory by the dentate gyrus (DG) [27]. This role of older DG granule cells in associative pattern completion is complemented by the finding that neurogenesis supports pattern separation by young DG granule cells [30]. Critically, for pattern completion in AM, it has been shown that patients with hippocampal lesions cannot recall nor imagine spatially coherent events [21], and this reconstructive process can be modelled at the level of neurons [8].…”

Section: The Role Of Hippocampus In Autobiographical Memorymentioning

confidence: 88%

“…-Pattern Separation. The process of transforming similar representations or memories into highly dissimilar, nonoverlapping representations [30]. This is important as we have many experiences that are similar to each other but nonetheless must be remembered as distinct.…”

Section: Characteristics Of Biological Autobiographical Memorymentioning

confidence: 99%

Machines Learning - Towards a New Synthetic Autobiographical Memory

Evans

Fox

Prescott

2014

Biomimetic and Biohybrid Systems

View full text Add to dashboard Cite

Abstract. Autobiographical memory is the organisation of episodes and contextual information from an individual's experiences into a coherent narrative, which is key to our sense of self. Formation and recall of autobiographical memories is essential for effective, adaptive behaviour in the world, providing contextual information necessary for planning actions and memory functions such as event reconstruction. A synthetic autobiographical memory system would endow intelligent robotic agents with many essential components of cognition through active compression and storage of historical sensorimotor data in an easily addressable manner. Current approaches neither fulfil these functional requirements, nor build upon recent understanding of predictive coding, deep learning, nor the neurobiology of memory. This position paper highlights desiderata for a modern implementation of synthetic autobiographical memory based on human episodic memory, and proposes that a recently developed model of hippocampal memory could be extended as a generalised model of autobiographical memory. Initial implementation will be targeted at social interaction, where current synthetic autobiographical memory systems have had success.

show abstract

“…Newborn neurons are also important for the induction of bidirectional hippocampal synaptic plasticity [16]. Furthermore, evidence is mounting to support the idea that adult-born neurons are integral participants in hippocampal-dependent cognitive processes, such as learning and memory formation [17][18][19], and mood regulation [20][21][22]. In this review, we consider the role of activity-dependent synaptic plasticity in regulating the activation of NSPC proliferation in the adult rodent hippocampus.…”

mentioning

confidence: 99%

The role of the N-methyl-d-aspartate receptor in the proliferation of adult hippocampal neural stem and precursor cells

Taylor

Bartlett

2014

Sci. China Life Sci.

View full text Add to dashboard Cite

New neurons are continuously generated from resident pools of neural stem and precursor cells (NSPCs) in the adult brain. There are multiple pathways through which adult neurogenesis is regulated, and here we review the role of the N-methyl-D-aspartate receptor (NMDAR) in regulating the proliferation of NSPCs in the adult hippocampus. Hippocampal-dependent learning tasks, enriched environments, running, and activity-dependent synaptic plasticity, all potently up-regulate hippocampal NSPC proliferation. We first consider the requirement of the NMDAR in activity-dependent synaptic plasticity, and the role the induction of synaptic plasticity has in regulating NSPCs and newborn neurons. We address how specific NMDAR agonists and antagonists modulate proliferation, both in vivo and in vitro, and then review the evidence supporting the hypothesis that NMDARs are present on NSPCs. We believe it is important to understand the mechanisms underlying the activation of adult neurogenesis, given the potential that endogenous stem cell populations have for repopulating the hippocampus with functional new neurons. In conditions such as age-related memory decline, neurodegeneration and psychiatric disease, mature neurons are lost or become defective; as such, stimulating adult neurogenesis may provide a therapeutic strategy to overcome these conditions. The adult brain continuously generates new neurons throughout life. These adult-born neurons arise from endogenous neural stem and precursor cells (NSPCs), which primarily reside within two neurogenic niches: the subgranular zone (SGZ) in the dentate gyrus (DG) of the hippocampus, and the subventricular zone (SVZ) of the lateral ventricles. In the 20 years since adult mammalian neurogenesis started receiving substantial attention [1,2], scientists have made great progress in understanding the mechanisms that regulate stem cell maintenance, proliferation, differentiation, maturation and integration [3,4]. Early on, extrinsic cues from the environment, such as learning [5], physical activity [6], and enriched environments [7,8], were found to potently enhance hippocampal neurogenesis. It was not long before a link was made to synaptic plasticity [9], which is also enhanced by physical exercise [10], and is widely accepted as the synaptic mechanism underlying hippocampal learning and memory [11]. Synaptic plasticity and adult hippocampal neurogenesis are intimately linked, as long-term potentiation (LTP), an activity-dependent change in synaptic efficacy, can influence the activation and proliferation of NSPCs in the DG (e.g., [12]), as well as the survival of newborn neurons (e.g., [13]). These newborn neurons have biophysical characteris-

show abstract

Young Dentate Granule Cells Mediate Pattern Separation, whereas Old Granule Cells Facilitate Pattern Completion

Cited by 725 publications

References 59 publications

Axonal ribosomes and mRNAs associate with fragile X granules in adult rodent and human brains

Axonal ribosomes and mRNAs associate with fragile X granules in adult rodent and human brains

Machines Learning - Towards a New Synthetic Autobiographical Memory

The role of the N-methyl-d-aspartate receptor in the proliferation of adult hippocampal neural stem and precursor cells

Contact Info

Product

Resources

About