Evidence map›Paper›PMID 35584727›Full record

ArticleNeurobiology of disease2022

Frequency-specific medial septal nucleus deep brain stimulation improves spatial memory in MK-801-treated male rats.

Nancy C Zepeda, Lindsey M Crown, Sasha Medvidovic, Wooseong Choi, Megha Sheth, Matthew Bergosh, Raymond Gifford, Caroline Folz, Phillip Lam, Gengxi Lu and 4 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neurobiology of disease, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.1field-weighted citation impact, top 26% 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

7 citing papers in PubMed, 10 citations in OpenAlex.

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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

14 authors at 2 institutions in 1 country.

Nancy C ZepedaDepartment of Neurological Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
Lindsey M CrownDepartment of Psychiatry and Behavioral Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
Sasha MedvidovicDepartment of Neurological Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
Wooseong ChoiDepartment of Neurological Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
Megha ShethDepartment of Neurological Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
Matthew BergoshDepartment of Neurological Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
Raymond GiffordDepartment of Psychiatry and Behavioral Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
Caroline FolzDepartment of Neurological Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
Phillip LamDepartment of Neurological Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
Gengxi LuDepartment of Biomedical Engineering, University of Southern California, Los Angeles, CA 90033, USA.
Robert FeatherstoneDepartment of Psychiatry and Behavioral Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
Charles Y LiuDepartment of Neurological Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA; Department of Biomedical Engineering, University of Southern California, Los Angeles, CA 90033, USA; USC Neurorestoration Center, Keck School of Medicine of USC, Los Angeles, USA.
Steven J SiegelDepartment of Psychiatry and Behavioral Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
Darrin J LeeDepartment of Neurological Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA; Department of Psychiatry and Behavioral Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA; Department of Biomedical Engineering, University of Southern California, Los Angeles, CA 90033, USA; USC Neurorestoration Center, Keck School of Medicine of USC, Los Angeles, USA. Electronic address: darrin.lee@med.usc.edu.
University of Southern California · USNeurological Surgery · US

Funding

Mentored Career DevelopmentKL2TR001854 · NCATS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI Elizabeth Rhea Erwin Burner, Amy Elizabeth West · 2016 to 2026
$9.0M
Septohippocampal circuit deep brain stimulation for selective RDoC aspects of cognitionK08MH121757 · NIMH · UNIVERSITY OF SOUTHERN CALIFORNIA · PI LEE, DARRIN JASON · 2020 to 2024
$982k
NCATS NIH HHS KL2 TR001854NIMH NIH HHS K08 MH121757
6 · The paper itself

Abstract

backgroundFew treatments exist for the cognitive symptoms of schizophrenia. Pharmacological agents resulting in glutamate N-methyl-d-aspartate (NMDA) receptor hypofunction, such as MK-801, mimic many of these symptoms and disrupt neural activity. Recent evidence suggests that deep brain stimulation (DBS) of the medial septal nucleus (MSN) can modulate medial prefrontal cortex (mPFC) and hippocampal activity and improve spatial memory.

objectiveHere, we examine the effects of acute MK-801 administration on oscillatory activity within the septohippocampal circuit and behavior. We also evaluate the potential for MSN stimulation to improve cognitive behavioral measures following MK-801 administration.

methods59 Sprague Dawley male rats received either acute intraperitoneal (IP) saline vehicle injections or MK-801 (0.1 mg/kg). Theta (5-12 Hz), low gamma (30-50 Hz) and high frequency oscillatory (HFO) power were analyzed in the mPFC, MSN, thalamus and hippocampus. Rats underwent MSN theta (7.7 Hz), gamma (100 Hz) or no stimulation during behavioral tasks (Novel object recognition (NOR), elevated plus maze, Barnes maze (BM)).

resultsInjection of MK-801 resulted in frequency-specific changes in oscillatory activity, decreasing theta while increasing HFO power. Theta, but not gamma, stimulation enhanced the anxiolytic effects of MK-801 on the elevated plus maze. While MK-801 treated rats exhibited spatial memory deficits on the Barnes maze, those that also received MSN theta, but not gamma, stimulation found the escape hole sooner.

conclusionsThese findings demonstrate that acute MK-801 administration leads to altered neural activity in the septohippocampal circuit and impaired spatial memory. Further, these findings suggest that MSN theta-frequency stimulation improves specific spatial memory deficits and may be a possible treatment for cognitive impairments caused by NMDA hypofunction.

Indexed as

Deep Brain StimulationSeptal NucleiAnimalsDizocilpine MaleateHippocampusMaleMemory DisordersN-MethylaspartateRatsRats, Sprague-DawleySpatial MemoryDizocilpine MaleateN-MethylaspartateDeep brain stimulationGammaHippocampusMedial septal nucleusMK-801Spatial working memorytheta

Identifiers

PMID35584727
PMCPMC9343054
OpenAlexW4280571178

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.