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André A. Fenton

Bio: André A. Fenton is an academic researcher from Center for Neural Science. The author has contributed to research in topics: Place cell & Dentate gyrus. The author has an hindex of 47, co-authored 169 publications receiving 8470 citations. Previous affiliations of André A. Fenton include New York University & State University of New York System.


Papers
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Journal ArticleDOI
28 Apr 2011-Nature
TL;DR: It is shown that inducible genetic expansion of the population of adult-born neurons through enhancing their survival improves performance in a specific cognitive task in which two similar contexts need to be distinguished, which is indicative of enhanced pattern separation.
Abstract: Adult hippocampal neurogenesis is a unique form of neural circuit plasticity that results in the generation of new neurons in the dentate gyrus throughout life. Neurons that arise in adults (adult-born neurons) show heightened synaptic plasticity during their maturation and can account for up to ten per cent of the entire granule cell population. Moreover, levels of adult hippocampal neurogenesis are increased by interventions that are associated with beneficial effects on cognition and mood, such as learning, environmental enrichment, exercise and chronic treatment with antidepressants. Together, these properties of adult neurogenesis indicate that this process could be harnessed to improve hippocampal functions. However, despite a substantial number of studies demonstrating that adult-born neurons are necessary for mediating specific cognitive functions, as well as some of the behavioural effects of antidepressants, it is unknown whether an increase in adult hippocampal neurogenesis is sufficient to improve cognition and mood. Here we show that inducible genetic expansion of the population of adult-born neurons through enhancing their survival improves performance in a specific cognitive task in which two similar contexts need to be distinguished. Mice with increased adult hippocampal neurogenesis show normal object recognition, spatial learning, contextual fear conditioning and extinction learning but are more efficient in differentiating between overlapping contextual representations, which is indicative of enhanced pattern separation. Furthermore, stimulation of adult hippocampal neurogenesis, when combined with an intervention such as voluntary exercise, produces a robust increase in exploratory behaviour. However, increasing adult hippocampal neurogenesis alone does not produce a behavioural response like that induced by anxiolytic agents or antidepressants. Together, our findings suggest that strategies that are designed to increase adult hippocampal neurogenesis specifically, by targeting the cell death of adult-born neurons or by other mechanisms, may have therapeutic potential for reversing impairments in pattern separation and dentate gyrus dysfunction such as those seen during normal ageing.

1,396 citations

Journal ArticleDOI
25 Aug 2006-Science
TL;DR: It is shown that a cell-permeable PKMz inhibitor, injected in the rat hippocampus, both reverses LTP maintenance in vivo and produces persistent loss of 1-day-old spatial information, indicating that the mechanism maintaining LTP sustains spatial memory.
Abstract: Analogous to learning and memory storage, long-term potentiation (LTP) is divided into induction and maintenance phases. Testing the hypothesis that the mechanism of LTP maintenance stores information requires reversing this mechanism in vivo and finding out whether long-term stored information is lost. This was not previously possible. Recently however, persistent phosphorylation by the atypical protein kinase C isoform, protein kinase Mzeta (PKMz), has been found to maintain late LTP in hippocampal slices. Here we show that a cell-permeable PKMz inhibitor, injected in the rat hippocampus, both reverses LTP maintenance in vivo and produces persistent loss of 1-day-old spatial information. Thus, the mechanism maintaining LTP sustains spatial memory.

831 citations

Journal ArticleDOI
06 Mar 2013-Neuron
TL;DR: It is demonstrated that GCs in the dorsal DG control exploratory drive and encoding, not retrieval, of contextual fear memories, and strategies aimed at modulating the excitability of the ventral DG may be beneficial for the treatment of anxiety disorders.

581 citations

Journal ArticleDOI
TL;DR: It is demonstrated here that firing is not nearly as reliable in the time domain as in the positional domain.
Abstract: The idea that the rat hippocampus stores a map of space is based on the existence of "place cells" that show "location-specific" firing. The discharge of place cells is confined with remarkable precision to a cell-specific part of the environment called the cell's "firing field." We demonstrate here that firing is not nearly as reliable in the time domain as in the positional domain. Discharge during passes through the firing field was compared with a model with Poisson variance of the location-specific firing determined by the time-averaged positional firing rate distribution. Place cells characteristically fire too little or too much compared with expectations from the random model. This fundamental property of place cells is referred to as "excess firing variance" and has three main implications: (i) Place cell discharge is not only driven by the summation of many small, asynchronous excitatory synaptic inputs. (ii) Place cell discharge may encode a signal in addition to the current head location. (iii) The excess firing variance helps explain why the errors in computing the rat's position from the simultaneous activity of many place cells are large.

283 citations

Journal ArticleDOI
TL;DR: It is demonstrated that adult neurogenesis contributes to cognitive flexibility when it requires changing a learned response to a stimulus‐evoked memory.
Abstract: The hippocampus is involved in segregating memories, an ability that utilizes the neural process of pattern separation and allows for cognitive flexibility. We evaluated a proposed role for adult hippocampal neurogenesis in cognitive flexibility using variants of the active place avoidance task and two independent methods of ablating adult-born neurons, focal X-irradiation of the hippocampus, and genetic ablation of glial fibrillary acidic protein positive neural progenitor cells, in mice. We found that ablation of adult neurogenesis did not impair the ability to learn the initial location of a shock zone. However, when conflict was introduced by switching the location of the shock zone to the opposite side of the room, irradiated and transgenic mice entered the new shock zone location significantly more than their respective controls. This impairment was associated with increased upregulation of the immediate early gene Arc in the dorsal dentate gyrus, suggesting a role for adult neurogenesis in modulating network excitability and/or synaptic plasticity. Additional experiments revealed that irradiated mice were also impaired in learning to avoid a rotating shock zone when it was added to an initially learned stationary shock zone, but were unimpaired in learning the identical simultaneous task variant if it was their initial experience with place avoidance. Impaired avoidance could not be attributed to a deficit in extinction or an inability to learn a new shock zone location in a different environment. Together these results demonstrate that adult neurogenesis contributes to cognitive flexibility when it requires changing a learned response to a stimulus-evoked memory.

274 citations


Cited by
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28 Jul 2005
TL;DR: PfPMP1)与感染红细胞、树突状组胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作�ly.
Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1(PfPMP1)与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员,通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

18,940 citations

01 Jan 1964
TL;DR: In this paper, the notion of a collective unconscious was introduced as a theory of remembering in social psychology, and a study of remembering as a study in Social Psychology was carried out.
Abstract: Part I. Experimental Studies: 2. Experiment in psychology 3. Experiments on perceiving III Experiments on imaging 4-8. Experiments on remembering: (a) The method of description (b) The method of repeated reproduction (c) The method of picture writing (d) The method of serial reproduction (e) The method of serial reproduction picture material 9. Perceiving, recognizing, remembering 10. A theory of remembering 11. Images and their functions 12. Meaning Part II. Remembering as a Study in Social Psychology: 13. Social psychology 14. Social psychology and the matter of recall 15. Social psychology and the manner of recall 16. Conventionalism 17. The notion of a collective unconscious 18. The basis of social recall 19. A summary and some conclusions.

5,690 citations

Journal ArticleDOI
TL;DR: A new framework for a more adequate theoretical treatment of perception and action planning is proposed, in which perceptual contents and action plans are coded in a common representational medium by feature codes with distal reference, showing that the main assumptions are well supported by the data.
Abstract: Traditional approaches to human information processing tend to deal with perception and action planning in isolation, so that an adequate account of the perception-action interface is still missing On the perceptual side, the dominant cognitive view largely underestimates, and thus fails to account for, the impact of action-related processes on both the processing of perceptual information and on perceptual learning On the action side, most approaches conceive of action planning as a mere continuation of stimulus processing, thus failing to account for the goal-directedness of even the simplest reaction in an experimental task We propose a new framework for a more adequate theoretical treatment of perception and action planning, in which perceptual contents and action plans are coded in a common representational medium by feature codes with distal reference Perceived events (perceptions) and to-be-produced events (actions) are equally represented by integrated, task-tuned networks of feature codes – cognitive structures we call event codes We give an overview of evidence from a wide variety of empirical domains, such as spatial stimulus-response compatibility, sensorimotor synchronization, and ideomotor action, showing that our main assumptions are well supported by the data

2,736 citations

Journal ArticleDOI
TL;DR: Lesions in distinct brain regions like hippocampus, striatum, basal forebrain, cerebellum and cerebral cortex were shown to impair MWM performance, but disconnecting rather than destroying brain regions relevant for spatial learning may impair M WM performance as well.

1,882 citations