Evidence map›Paper›PMID 30100256›Full record

ArticleNeuron2018

A Highly Sensitive A-Kinase Activity Reporter for Imaging Neuromodulatory Events in Awake Mice.

Lei Ma, Bart C Jongbloets, Wei-Hong Xiong, Joshua B Melander, Maozhen Qin, Tess J Lameyer, Madeleine F Harrison, Boris V Zemelman, Tianyi Mao, Haining Zhong

Erratum issuedOpen access · bronzeAbstract read
In one paragraph

Article in Neuron, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 64 papers.

0numbers the graph read from it
0cells of the map it votes in
64citing papers in PubMed
4.5field-weighted citation impact, top 4% 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

64 citing papers in PubMed, 99 citations in OpenAlex.

  1. Article
  2. A molecular integrator of sleep duration and interruption.bioRxiv : the preprint server for biology · 2026
    Article
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  6. Article
  7. Sensitive and Selective Next-Generation FRET-based PKA Biosensors.bioRxiv : the preprint server for biology · 2026
    Article
  8. Adenosine in the Brain: Recent Progress on Detection, Function, and Translation.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025
    Review
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  18. Review
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4 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 3 institutions in 1 country.

Lei MaVollum Institute, Oregon Health & Science University, Portland, OR 97239, USA.
Bart C JongbloetsVollum Institute, Oregon Health & Science University, Portland, OR 97239, USA.
Wei-Hong XiongVollum Institute, Oregon Health & Science University, Portland, OR 97239, USA.
Joshua B MelanderVollum Institute, Oregon Health & Science University, Portland, OR 97239, USA.
Maozhen QinVollum Institute, Oregon Health & Science University, Portland, OR 97239, USA.
Tess J LameyerVollum Institute, Oregon Health & Science University, Portland, OR 97239, USA.
Madeleine F HarrisonCenter for Learning and Memory, The University of Texas at Austin, Austin, TX 78712, USA.
Boris V ZemelmanCenter for Learning and Memory, The University of Texas at Austin, Austin, TX 78712, USA.
Tianyi MaoVollum Institute, Oregon Health & Science University, Portland, OR 97239, USA. Electronic address: mao@ohsu.edu.
Haining ZhongVollum Institute, Oregon Health & Science University, Portland, OR 97239, USA. Electronic address: zhong@ohsu.edu.
Oregon Health & Science University · USVollum Institute · USThe University of Texas at Austin · US

Funding

Multiplex imaging of neuronal activity and signaling dynamics underlying learning in discrete amygdala circuits of behaving mice.R01NS104944 · NINDS · OREGON HEALTH & SCIENCE UNIVERSITY · PI LI, BO, MAO, TIANYI · 2018 to 2022
$5.0M
Genetic and physiological dissection of the circuit mechanisms in the striatum.R01NS081071 · NINDS · OREGON HEALTH & SCIENCE UNIVERSITY · PI MAO, TIANYI · 2013 to 2023
$3.6M
A novel approach to examine slow synaptic transmission in vivoU01NS094247 · NINDS · OREGON HEALTH & SCIENCE UNIVERSITY · PI MAO, TIANYI, ZHONG, HAINING · 2015 to 2018
$1.3M
Fluorescence labeling of PSD-95 at endogenous levels for single cell imagingR21NS084315 · NINDS · OREGON HEALTH & SCIENCE UNIVERSITY · PI ZHONG, HAINING · 2014 to 2015
$424k
Fluorescence labeling of synaptic proteins for cell-specific imaging in vivoR21NS097856 · NINDS · OREGON HEALTH & SCIENCE UNIVERSITY · PI ZHONG, HAINING · 2016 to 2017
$424k
NINDS NIH HHS R01 NS081071NINDS NIH HHS R01 NS104944NINDS NIH HHS R21 NS084315NINDS NIH HHS R21 NS097856NINDS NIH HHS U01 NS094247
6 · The paper itself

Abstract

Neuromodulation imposes powerful control over brain function, and cAMP-dependent protein kinase (PKA) is a central downstream mediator of multiple neuromodulators. Although genetically encoded PKA sensors have been developed, single-cell imaging of PKA activity in living mice has not been established. Here, we used two-photon fluorescence lifetime imaging microscopy (2pFLIM) to visualize genetically encoded PKA sensors in response to the neuromodulators norepinephrine and dopamine. We screened available PKA sensors for 2pFLIM and further developed a variant (named tAKARα) with increased sensitivity and a broadened dynamic range. This sensor allowed detection of PKA activation by norepinephrine at physiologically relevant concentrations and kinetics, and by optogenetically released dopamine. In vivo longitudinal 2pFLIM imaging of tAKARα tracked bidirectional PKA activities in individual neurons in awake mice and revealed neuromodulatory PKA events that were associated with wakefulness, pharmacological manipulation, and locomotion. This new sensor combined with 2pFLIM will enable interrogation of neuromodulation-induced PKA signaling in awake animals. VIDEO ABSTRACT.

Indexed as

AnimalsAnimals, NewbornCyclic AMP-Dependent Protein KinasesEnzyme ActivationFemaleHippocampusMaleMiceMice, Inbred C57BLMicroscopy, Fluorescence, MultiphotonNeurotransmitter AgentsNorepinephrineOrgan Culture TechniquesWakefulnessCyclic AMP-Dependent Protein KinasesNeurotransmitter AgentsNorepinephrineA Kinase Activity Reporter (AKAR)cAMP dependent kinase (PKA)dopamineenforced locomotionForster resonance energy transfer (FRET)in vivo imagingneuromodulationnorepinephrinetwo-photon fluorescence lifetime imaging (2pFLIM)wakefulness

Identifiers

PMID30100256
PMCPMC6152931
OpenAlexW2886118005

What OpenQuestion holds

Textmetadata
LicenceTDM
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.