Evidence map›Paper›PMID 25891221›Full record

ReviewBiological psychiatry2015

Delta frequency optogenetic stimulation of the thalamic nucleus reuniens is sufficient to produce working memory deficits: relevance to schizophrenia.

Aranda R Duan, Carmen Varela, Yuchun Zhang, Yinghua Shen, Lealia Xiong, Matthew A Wilson, John Lisman

Abstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Biological psychiatry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

44 citing papers in PubMed, 1 synthesis or guideline pooled it.

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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

7 authors.

Aranda R DuanBrandeis University, Waltham, Massachusetts.
Carmen VarelaThe Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, Massachusetts.
Yuchun ZhangBrandeis University, Waltham, Massachusetts.
Yinghua ShenThe Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, Massachusetts.
Lealia XiongBrandeis University, Waltham, Massachusetts; The Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, Massachusetts.
Matthew A WilsonThe Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, Massachusetts.
John LismanBrandeis University, Waltham, Massachusetts. Electronic address: lisman@brandeis.edu.

Funding

Quantitative Neuroscience: Tools for Bridging Levels of AnalysisT32NS007292 · NINDS · BRANDEIS UNIVERSITY · PI GINA G TURRIGIANO · 1986 to 2026
$12.7M
Redesigning General Anesthesia (Admin Supp)R01GM104948 · NIGMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI BOYDEN, EDWARD S., BROWN, EMERY N · 2012 to 2016
$4.4M
Role of NMDA receptors in awake-state thalamocortical slow wavesR01MH086518 · NIMH · BRANDEIS UNIVERSITY · PI LISMAN, JOHN E · 2010 to 2014
$2.0M
NIGMS NIH HHS 1-R01-GM104948-02NIGMS NIH HHS R01 GM104948NIMH NIH HHS R01 MH086518NIMH NIH HHS R01MH086581NINDS NIH HHS T32 NS007292NINDS NIH HHS T32NS007292-28
6 · The paper itself

Abstract

backgroundLow-frequency (delta/theta) oscillations in the thalamocortical system are elevated in schizophrenia during wakefulness and are also induced in the N-methyl-D-asparate receptor hypofunction rat model. To determine whether abnormal delta oscillations might produce functional deficits, we used optogenetic methods in awake rats. We illuminated channelrhodopsin-2 in the thalamic nucleus reuniens (RE) at delta frequency and measured the effect on working memory (WM) performance (the RE is involved in WM, a process affected in schizophrenia [SZ]).

methodsWe injected RE with adeno-associated virus to transduce cells with channelrhodopsin-2. An optical fiber was implanted just dorsal to the hippocampus in order to illuminate RE axon terminals.

resultsDuring optogenetic delta frequency stimulation, rats displayed a strong WM deficit. On the following day, performance was normal if illumination was omitted.

conclusionsThe optogenetic experiments show that delta frequency stimulation of a thalamic nucleus is sufficient to produce deficits in WM. This result supports the hypothesis that delta frequency bursting in particular thalamic nuclei has a causal role in producing WM deficits in SZ. The action potentials in these bursts may "jam" communication through the thalamus, thereby interfering with behaviors dependent on WM. Studies in thalamic slices using the N-methyl-D-asparate receptor hypofunction model show that delta frequency bursting is dependent on T-type Ca(2+) channels, a result that we confirmed here in vivo. These channels, which are strongly implicated in SZ by genome-wide association studies, may thus be a therapeutic target for treatment of SZ.

Indexed as

Schizophrenic PsychologyAnimalsDelta RhythmHippocampusMaleMemory DisordersMemory, Short-TermMidline Thalamic NucleiOptogeneticsRatsRats, Long-EvansSchizophreniaChannelrhodopsinDeltaOptogeneticsReuniensSchizophreniaThalamus

Identifiers

PMID25891221
PMCPMC4444380

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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.