Evidence map›Paper›PMID 36471155›Full record

ArticleScientific reports2022

Disruption of hippocampal neuronal circuit function depends upon behavioral state in the APP/PS1 mouse model of Alzheimer's disease.

Heng Zhou, Hanyan Li, Niket Gowravaram, Moqin Quan, Naila Kausar, Stephen N Gomperts

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
2.7field-weighted citation impact, top 9% 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

18 citing papers in PubMed, 24 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. Review
  12. Review
  13. Distinct synaptic mechanisms drive the behavioral response to acute stress and rapid correction by ketamine.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024
    Article
  14. Article
  15. Article
  16. Review
  17. Article
  18. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 2 countries.

Heng Zhou *MassGeneral Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital, Charlestown, MA, USA.
Hanyan Li *MassGeneral Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital, Charlestown, MA, USA.
Niket GowravaramMassGeneral Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital, Charlestown, MA, USA.
Moqin QuanMassGeneral Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital, Charlestown, MA, USA.
Naila KausarMassGeneral Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital, Charlestown, MA, USA.
Stephen N GompertsMassGeneral Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital, Charlestown, MA, USA. Gomperts.stephen@mgh.harvard.edu.
MaineGeneral Medical Center · USMassachusetts General Hospital · US

Funding

Neural Circuit Disruption in Freely-Behaving models of Alzheimer's Disease.R01AG077611 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI Stephen N. Gomperts · 2022 to 2026
$3.8M
Impact of Amyloid Beta on Hippocampal Neurophysiology and Calcium Activity across the Sleep-Wake CycleR01AG054551 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI GOMPERTS, STEPHEN N. · 2017 to 2021
$2.1M
NIA NIH HHS R01 AG054551NIA NIH HHS R01 AG077611
6 · The paper itself

Abstract

The Alzheimer's disease-associated peptide amyloid-beta (Aβ) has been associated with neuronal hyperactivity under anesthesia, but clinical trials of anticonvulsants or neural system suppressors have, so far, failed to improve symptoms in AD. Using simultaneous hippocampal calcium imaging and electrophysiology in freely moving mice expressing human Aβ, here we show that Aβ aggregates perturbed neural systems in a state-dependent fashion, driving neuronal hyperactivity in exploratory behavior and slow wave sleep (SWS), yet suppressing activity in quiet wakefulness (QW) and REM sleep. In exploratory behavior and REM sleep, Aβ impaired hippocampal theta-gamma phase-amplitude coupling and altered neuronal synchronization with theta. In SWS, Aβ reduced cortical slow oscillation (SO) power, the coordination of hippocampal sharp wave-ripples with both the SO and thalamocortical spindles, and the coordination of calcium transients with the sharp wave-ripple. Physostigmine improved Aβ-associated hyperactivity in exploratory behavior and hypoactivity in QW and expanded the range of gamma that coupled with theta phase, but exacerbated hypoactivity in exploratory behavior. Together, these findings show that the effects of Aβ alone on hippocampal circuit function are profoundly state dependent and suggest a reformulation of therapeutic strategies aimed at Aβ induced hyperexcitability.

Indexed as

Alzheimer DiseaseAmyloid beta-PeptidesHippocampusAnimalsCalciumDisease Models, AnimalHumansMiceMice, TransgenicAmyloid beta-PeptidesCalcium

Identifiers

PMID36471155
PMCPMC9723144
OpenAlexW4311288821

What OpenQuestion holds

Textmetadata
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.