The hippocampus plays a critical role at encoding discontiguous events for subsequent declarative memory expression in mice

Mingaud, Frédérique; Moine, Catherine Le; Etchamendy, Nicole; Mormède, Cécile; Jaffard, Robert; Marighetto, Aline

doi:10.1002/hipo.20262

Cited by 19 publications

(18 citation statements)

References 46 publications

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“…In this paradigm, the age-related impairment in flexible memory expression (as revealed by stage 2 testing) was shown recently to derive from a primary STWM decline during (stage 1) learning; this STWM deficit was associated with an hypoactivity of the (hippocampo-prefrontal) declarative memory system and was believed to hinder relational encoding of individual arm experiences made during learning, into a unified LTDM representation (Mingaud et al, 2007) (our unpublished data).…”

Section: Experiments 3a and 3b: Vitamin A Supplementation Effects On mentioning

confidence: 79%

“…The selective two-choice deficit is interpreted as a loss in the ability to encode individual arm experiences into a relational representation sustaining mnemonic flexibility, i.e., LTDM (Cohen and Eichenbaum, 1993;Eichenbaum, 2004), with the sparing of procedural learning capabilities relying on rigid and separate memory representations (for aged monkeys, see also Rapp et al, 1996). As demonstrated recently (Mingaud et al, 2007) and further confirmed by present Fos imaging data, mnemonic inflexibility as revealed by stage 2 testing is associated with a defect in (stage 1) learning-induced activation of hippocampal and prefrontal areas, known for subserving declarative memory.…”

Section: Hippocampal Retinoid Signaling Hypoexpression Is Associated mentioning

confidence: 99%

“…TM training is used as control condition for measuring neuronal activity unrelated to memory processes engaged by RAM tasks (cf. Touzani et al, 2003;Mingaud et al, 2007). Both apparatus were located in the same room, and each TM mouse was run in parallel with an RAM mouse.…”

Section: Experiments 3a and 3b: Vitamin A Supplementation Effects On mentioning

confidence: 99%

“…7 A, B, 8A, B). This specific loss of mnemonic flexibility, revealed by a test situation demanding an explicit comparison between separately acquired information, has been proposed as a mouse model for the preferential declarative memory loss in senescence (Marighetto et al, 1999(Marighetto et al, , 2000 and in association with hippocampal dysfunction (Etchamendy et al, 2001(Etchamendy et al, , 2003Touzani et al, 2003;Mingaud et al, 2007). The deficit selectivity enables us to rule out trivial explanations (such as deterioration in motivation, perception, and locomotion) for observed changes in behavior (and concomitant brain activity, see below) in the aged mice.…”

Section: Hippocampal Retinoid Signaling Hypoexpression Is Associated mentioning

confidence: 99%

“…We speculated that faster decay of incoming event traces in (hippocampo-prefrontal) short-term episodic buffer may hinder relational encoding of temporally discontiguous events into a unified mnemonic representation sustaining LTDM (Wallenstein et al, 1998;Eichenbaum, 2004;Mingaud et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

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Retinoid Hyposignaling Contributes to Aging-Related Decline in Hippocampal Function in Short-Term/Working Memory Organization and Long-Term Declarative Memory Encoding in Mice

Mingaud¹,

Mormède²,

Etchamendy³

et al. 2008

J. Neurosci.

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An increasing body of evidence indicates that the vitamin A metabolite retinoic acid (RA) plays a role in adult brain plasticity by activating gene transcription through nuclear receptors. Our previous studies in mice have shown that a moderate downregulation of retinoidmediated transcription contributed to aging-related deficits in hippocampal long-term potentiation and long-term declarative memory (LTDM). Here, knock-out, pharmacological, and nutritional approaches were used in a series of radial-arm maze experiments with mice to further assess the hypothesis that retinoid-mediated nuclear events are causally involved in preferential degradation of hippocampal function in aging. Molecular and behavioral findings confirmed our hypothesis. First, a lifelong vitamin A supplementation, like shortterm RA administration, was shown to counteract the aging-related hippocampal (but not striatal) hypoexpression of a plasticity-related retinoid target-gene, GAP43 (reverse transcription-PCR analyses, experiment 1), as well as short-term/working memory (STWM) deterioration seen particularly in organization demanding trials (STWM task, experiment 2). Second, using a two-stage paradigm of LTDM, we demonstrated that the vitamin A supplementation normalized memory encoding-induced recruitment of (hippocampo-prefrontal) declarative memory circuits, without affecting (striatal) procedural memory system activity in aged mice (Fos neuroimaging, experiment 3A) and alleviated their LTDM impairment (experiment 3B). Finally, we showed that (knock-out, experiment 4) RA receptor ␤ and retinoid X receptor ␥, known to be involved in STWM (Wietrzych et al., 2005), are also required for LTDM. Hence, aging-related retinoid signaling hypoexpression disrupts hippocampal cellular properties critically required for STWM organization and LTDM formation, and nutritional vitamin A supplementation represents a preventive strategy. These findings are discussed within current neurobiological perspectives questioning the historical consensus on STWM and LTDM system partition.

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Section: Experiments 3a and 3b: Vitamin A Supplementation Effects On mentioning

confidence: 79%

Section: Hippocampal Retinoid Signaling Hypoexpression Is Associated mentioning

confidence: 99%

Section: Experiments 3a and 3b: Vitamin A Supplementation Effects On mentioning

confidence: 99%

Section: Hippocampal Retinoid Signaling Hypoexpression Is Associated mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Retinoid Hyposignaling Contributes to Aging-Related Decline in Hippocampal Function in Short-Term/Working Memory Organization and Long-Term Declarative Memory Encoding in Mice

Mingaud¹,

Mormède²,

Etchamendy³

et al. 2008

J. Neurosci.

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The hippocampus contributes to memory expression during transitive inference in mice

2009

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There is substantial evidence that the hippocampus plays a role in transitive inference, the capacity to link overlapping memories and subsequently make novel judgments between elements of those memories that are only indirectly related. However, it is unclear whether the hippocampus is involved primarily during the original acquisition of the overlapping memories, or additionally during the flexible expression of those memories during transitive judgments. Here, we demonstrated that selective hippocampal damage produced after acquisition of the overlapping memories resulted in a severe impairment in subsequent transitive inference judgments, indicating that the hippocampus does play an important role beyond the initial learning phase. Furthermore, this study extends to mice a role for the hippocampus in transitive inference, as previously observed in other species.

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Evidence for a virtual human analog of a rodent relational memory task: A study of aging and fMRI in young adults

et al. 2011

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A radial maze concurrent spatial discrimination learning paradigm consisting of two stages was previously designed to assess the flexibility property of relational memory in mice, as a model of human declarative memory. Aged mice and young adult mice with damage to the hippocampus, learned accurately Stage 1 of the task which required them to learn a constant reward location in a specific set of arms (i.e., learning phase). In contrast, they were impaired relative to healthy young adult mice in a second stage when faced with rearrangements of the same arms (i.e., flexibility probes). This mnemonic inflexibility in Stage 2 is thought to derive from insufficient relational processing by the hippocampus during initial learning (Stage 1) which favors stimulus-response learning, a form of procedural learning. This was proposed as a model of the selective declarative and relational memory decline classically described in elderly people. As a first step to examine the validity of this model, we adapted this protocol to humans using a virtual radial-maze. (1) We showed that performance in the flexibility probes in young and older adults positively correlated with performance in a wayfinding task, suggesting that our paradigm assesses relational memory. (2) We demonstrated that older healthy participants displayed a deficit in the performance of the flexibility probes (Stage 2), similar to the one previously seen in aged mice. This was associated with a decline in the wayfinding task. (3) Our fMRI data in young adults confirmed that hippocampal activation during early discrimination learning in Stage 1 correlated with memory flexibility in Stage 2, whereas caudate nucleus activation in Stage 1 negatively correlated with subsequent flexibility. By enabling relational memory assessment in mice and humans, our radial-maze paradigm provides a valuable tool for translational research.

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The hippocampus plays a critical role at encoding discontiguous events for subsequent declarative memory expression in mice

Cited by 19 publications

References 46 publications

Retinoid Hyposignaling Contributes to Aging-Related Decline in Hippocampal Function in Short-Term/Working Memory Organization and Long-Term Declarative Memory Encoding in Mice

Retinoid Hyposignaling Contributes to Aging-Related Decline in Hippocampal Function in Short-Term/Working Memory Organization and Long-Term Declarative Memory Encoding in Mice

The hippocampus contributes to memory expression during transitive inference in mice

Evidence for a virtual human analog of a rodent relational memory task: A study of aging and fMRI in young adults

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