Evidence map›Paper›PMID 38130024›Full record

ArticleAging cell2024

Genetic context drives age-related disparities in synaptic maintenance and structure across cortical and hippocampal neuronal circuits.

Sarah E Heuer, Emily W Nickerson, Gareth R Howell, Erik B Bloss

Open access · goldAbstract read
In one paragraph

Article in Aging cell, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.0field-weighted citation impact, top 25% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 7 citations in OpenAlex.

  1. Review
  2. Consciousness, subjectivity, and aging in western thought.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026
    Review
  3. Review
  4. Article
  5. Genetic context modulates aging and degeneration in the murine retina.bioRxiv : the preprint server for biology · 2024
    Article
  6. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

4 authors at 1 institution in 1 country.

Sarah E HeuerThe Jackson Laboratory, Bar Harbor, Maine, USA.ORCID 0000-0003-4461-2386
Emily W NickersonThe Jackson Laboratory, Bar Harbor, Maine, USA.ORCID 0000-0002-0397-6514
Gareth R HowellThe Jackson Laboratory, Bar Harbor, Maine, USA.ORCID 0000-0003-0565-6474
Erik B BlossThe Jackson Laboratory, Bar Harbor, Maine, USA.ORCID 0000-0001-5031-4591
Tufts University · US

Funding

The IU/JAX Alzheimer's Disease Precision Models Center: Rat F344U54AG054345 · NIA · INDIANA UNIVERSITY INDIANAPOLIS · PI Gregory W Carter, Gareth R Howell · 2016 to 2026
$95.6M
Systems Genetics Approach to Determine Interactors of Apolipoprotein E in Alzheimer’s DiseaseRF1AG055104 · NIA · JACKSON LABORATORY · PI CARTER, GREGORY W, HOWELL, GARETH R · 2018 to 2018
$4.1M
Deconstruction of a Hypothalamic Exercise-responsive Circuit for NeuroprotectionR01AG079877 · NIA · JACKSON LABORATORY · PI Erik Bradley Bloss · 2023 to 2026
$3.1M
Training Program in Precision Genetics of Aging, Alzheimer's Disease and Related DementiasT32AG062409 · NIA · JACKSON LABORATORY · PI Gareth R Howell, KRISTEN M O'CONNELL · 2020 to 2026
$1.5M
NIA NIH HHS AG055104NIA NIH HHS AG062409NIA NIH HHS AG079877NIA NIH HHS R01 AG079877NIA NIH HHS RF1 AG055104NIA NIH HHS T32 AG062409NIA NIH HHS U54 AG054345
6 · The paper itself

Abstract

The disconnection of neuronal circuitry through synaptic loss is presumed to be a major driver of age-related cognitive decline. Age-related cognitive decline is heterogeneous, yet whether genetic mechanisms differentiate successful from unsuccessful cognitive decline through maintenance or vulnerability of synaptic connections remains unknown. Previous work using rodent and primate models leveraged various techniques to imply that age-related synaptic loss is widespread on pyramidal cells in prefrontal cortex (PFC) circuits but absent on those in area CA1 of the hippocampus. Here, we examined the effect of aging on synapses on projection neurons forming a hippocampal-cortico-thalamic circuit important for spatial working memory tasks from two genetically distinct mouse strains that exhibit susceptibility (C57BL/6J) or resistance (PWK/PhJ) to cognitive decline during aging. Across both strains, synapse density on CA1-to-PFC projection neurons appeared completely intact with age. In contrast, we found synapse loss on PFC-to-nucleus reuniens (RE) projection neurons from aged C57BL/6J but not PWK/PhJ mice. Moreover, synapses from aged PWK/PhJ mice but not from C57BL/6J exhibited altered morphologies that suggest increased efficiency to drive depolarization in the parent dendrite. Our findings suggest resistance to age-related cognitive decline results in part by age-related synaptic adaptations, and identification of these mechanisms in PWK/PhJ mice could uncover new therapeutic targets for promoting successful cognitive aging and extending human health span.

Indexed as

HippocampusNeuronsAgedAnimalsHumansMiceMice, Inbred C57BLNeuronal PlasticityPyramidal CellsSynapsesagingfrontal cortexgenetic diversityneuronal circuitssynaptic plasticity

Identifiers

PMID38130024
PMCPMC10861192
OpenAlexW4390110701

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.