Neurocognitive Aging and the Hippocampus across Species

Leal, Stephanie L.; Yassa, Michael A.

doi:10.1016/j.tins.2015.10.003

Cited by 177 publications

(167 citation statements)

References 133 publications

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“…However, given that many older adults exhibit tau pathology in the absence of an AD diagnosis (49), an alternate explanation for this hyperactivity is hippocampal excitotoxicity associated with AD pathology (55,56). Alternatively, findings in aged rodents indicate that memory deficits associated with hippocampal hyperactivity may result from dysfunction of inhibitory interneurons (8,9). Taken together, these findings suggest that DG/CA3 hyperactivity negatively affects memory performance, but the underlying mechanisms of this increased activity remain underspecified.…”

Section: Discussionmentioning

confidence: 99%

“…If individual subfields are differentially vulnerable to age-related change, then averaging activity across regions could produce variable findings. Importantly, research in aged rodents suggests focal changes, indicating selective synaptic weakening among perforant path inputs from ERC to DG and CA3, as well as representational rigidity in CA3 place cells (8,9,11).…”

Section: Significancementioning

confidence: 99%

“…1A). Moreover, evidence in rodents and humans suggests that these subfields are differentially affected by age, as well as by age-related disease (8,9,11).…”

mentioning

confidence: 99%

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Individual differences in associative memory among older adults explained by hippocampal subfield structure and function

Carr

Bernstein

Favila

et al. 2017

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

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Older adults experience impairments in episodic memory, ranging from mild to clinically significant. Given the critical role of the medial temporal lobe (MTL) in episodic memory, age-related changes in MTL structure and function may partially account for individual differences in memory. Using ultra-high-field 7T structural MRI and high-resolution 3T functional MRI (hr-fMRI), we evaluated MTL subfield thickness and function in older adults representing a spectrum of cognitive health. Participants performed an associative memory task during hr-fMRI in which they encoded and later retrieved face-name pairs. Motivated by prior research, we hypothesized that differences in performance would be explained by the following: (i) entorhinal cortex (ERC) and CA1 apical neuropil layer [CA1-stratum radiatum lacunosum moleculare (SRLM)] thickness, and (ii) activity in ERC and the dentate gyrus (DG)/CA3 region. Regression analyses revealed that this combination of factors significantly accounted for variability in memory performance. Among these metrics, CA1-SRLM thickness was positively associated with memory, whereas DG/CA3 retrieval activity was negatively associated with memory. Furthermore, including structural and functional metrics in the same model better accounted for performance than did single-modality models. These results advance the understanding of how independent but converging influences of both MTL subfield structure and function contribute to age-related memory impairment, complementing findings in the rodent and human postmortem literatures.episodic memory | hippocampus | aging | mild cognitive impairment | Alzheimer's disease E pisodic memory, or the capacity to encode and subsequently retrieve memories for events, is known to be particularly vulnerable to age-related change (1-3). Older adults show varying degrees of episodic memory impairment, ranging from mild to clinically significant. One potential factor underlying such differences is variability in the structure and function of the medial temporal lobe (MTL).The MTL is essential for episodic memory (4-7), and research across species indicates that the MTL changes in both healthy aging and in age-related neurodegenerative disease (for reviews, see refs. 8 and 9). Critically, however, the MTL is not a unitary structure. Rather, it is composed of multiple regions with differing anatomy and connectivity (see, e.g., ref. 10), including subfields of the hippocampal formation [CA1, CA2, CA3, dentate gyrus (DG), and subiculum], and the entorhinal (ERC), perirhinal (PRC), and parahippocampal (PHC) cortices (Fig. 1A). Moreover, evidence in rodents and humans suggests that these subfields are differentially affected by age, as well as by age-related disease (8, 9, 11).Converging evidence in human studies of healthy aging using high-resolution magnetic resonance imaging (MRI) suggests disproportionate age-related atrophy in CA1 (12-15), although some studies point to selective atrophy of the subiculum or DG/CA3, while others suggest changes encompassing multip...

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Section: Discussionmentioning

confidence: 99%

Section: Significancementioning

confidence: 99%

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Individual differences in associative memory among older adults explained by hippocampal subfield structure and function

Carr

Bernstein

Favila

et al. 2017

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

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“…There is extensive evidence that declining memory function is present with increasing age 69–71 and is a major symptom of mild cognitive impairment (MCI) and Alzheimer’s disease (AD). Convergent data across animal and human studies have suggested that a key neural substrate for this decline is a shift in hippocampal network dynamics away from pattern separation and toward pattern com- pletion 72 , which appears to be mediated by CA3 hyperactivity 35,73–76 and representational rigidity 35,72,75,77 —a failure to remap or manifest a novelty signal when stimuli are similar but not identical.…”

Section: Age-related Cognitive Decline and Dementiamentioning

confidence: 99%

Integrating new findings and examining clinical applications of pattern separation

2018

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Pattern separation, the ability to independently represent and store similar experiences, is a crucial facet of episodic memory. Growing evidence suggests that the hippocampus possesses unique circuitry that is computationally capable of resolving mnemonic interference by using pattern separation. In this Review, we discuss recent advances in the understanding of this process and evaluate the caveats and limitations of linking across animal and human studies. We summarize clinical and translational studies using methods that are sensitive to pattern separation impairments, an approach that stems from the fact that the hippocampus is a major site of disruption in many brain disorders. We critically evaluate the assumptions that guide fundamental and translational studies in this area. Finally, we suggest guidelines for future research and offer ways to overcome potential interpretational challenges to increase the utility of pattern separation as a construct that can further understanding of both memory processes and brain disease.

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“…However, the striking similarities in the hippocampal cytoarchitecture of different species were apparent in the studies of the early anatomists (Ramón y Cajal, 1911;Lorente de Nó, 1947). Nowadays a cross-species consensus is beginning to emerge (Leal and Yassa, 2015) regarding hippocampal function and organization. Modern and advanced techniques (e.g.…”

Section: Anatomy and Connectivitymentioning

confidence: 99%

Investigation of the hippocampal information processing in freely moving rats

Gonzalez¹

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Neurocognitive Aging and the Hippocampus across Species

Cited by 177 publications

References 133 publications

Individual differences in associative memory among older adults explained by hippocampal subfield structure and function

Individual differences in associative memory among older adults explained by hippocampal subfield structure and function

Integrating new findings and examining clinical applications of pattern separation

Investigation of the hippocampal information processing in freely moving rats

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