Evidence map›Paper›PMID 40707359›Full record

ArticleeNeuro2025

Dopamine Receptor 1 Specific CRISPRa Mice Exhibit Disrupted Behaviors and Striatal Baseline Cellular Activity.

Rianne R Campbell, Mikah Green, Eric Y Choi, Andreas B Wulff, Allison N Siclair, Smirti Khatri, Geralin Virata, Christina Barrett, Symphanie Key, Samir Patel and 5 more

Abstract read
In one paragraph

Article in eNeuro, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–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

2 citing papers in PubMed.

  1. Article
  2. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors.

Rianne R CampbellDepartments of Neurobiology, University of Maryland School of Medicine, Baltimore, Maryland 21201.
Mikah GreenDepartments of Neurobiology, University of Maryland School of Medicine, Baltimore, Maryland 21201.ORCID https://orcid.org/0000-0003-4886-2040
Eric Y ChoiDepartments of Neurobiology, University of Maryland School of Medicine, Baltimore, Maryland 21201.ORCID https://orcid.org/0000-0002-0023-6844
Andreas B WulffPharmacology and Physiology, University of Maryland School of Medicine, Baltimore, Maryland 21201.ORCID https://orcid.org/0000-0002-5610-4330
Allison N SiclairPharmacology and Physiology, University of Maryland School of Medicine, Baltimore, Maryland 21201.
Smirti KhatriDepartments of Neurobiology, University of Maryland School of Medicine, Baltimore, Maryland 21201.
Geralin VirataDepartments of Neurobiology, University of Maryland School of Medicine, Baltimore, Maryland 21201.
Christina BarrettDepartments of Neurobiology, University of Maryland School of Medicine, Baltimore, Maryland 21201.
Symphanie KeyDepartments of Neurobiology, University of Maryland School of Medicine, Baltimore, Maryland 21201.
Samir PatelDepartments of Neurobiology, University of Maryland School of Medicine, Baltimore, Maryland 21201.ORCID https://orcid.org/0009-0006-0048-0667
Mary Beth RowellDepartments of Neurobiology, University of Maryland School of Medicine, Baltimore, Maryland 21201.
Daniela FrancoDepartments of Neurobiology, University of Maryland School of Medicine, Baltimore, Maryland 21201.
Shanmugasundaram Ganapathy-KanniappanDepartments of Neurobiology, University of Maryland School of Medicine, Baltimore, Maryland 21201.
Brian N MathurPharmacology and Physiology, University of Maryland School of Medicine, Baltimore, Maryland 21201.
Mary Kay LoboDepartments of Neurobiology, University of Maryland School of Medicine, Baltimore, Maryland 21201 mklobo@som.umaryland.edu.ORCID https://orcid.org/0000-0002-9419-2079

Funding

Cocaine-induced mitochondrial mechanisms and molecular mediators in reward circuitryR01DA038613 · NIDA · UNIVERSITY OF MARYLAND BALTIMORE · PI LOBO, MARY KAY · 2014 to 2025
$4.9M
Epigenome Editing in Opioid ActionR33DA052101 · NIDA · UNIVERSITY OF MARYLAND BALTIMORE · PI Mary Kay Lobo · 2024 to 2026
$927k
NIDA NIH HHS R01 DA038613NIDA NIH HHS R33 DA052101
6 · The paper itself

Abstract

The two main cell types in the striatum, dopamine receptor 1 and adenosine receptor 2a spiny projection neurons (D1-SPNs and A2A-SPNs), have distinct roles in regulating motor- and reward-related behaviors. Cre-selective CRISPR-dCas9 systems allow for cell-type specific, epigenomic-based manipulation of gene expression with gene-specific single guide RNAs (sgRNAs) and have potential to elucidate molecular mechanisms underlying striatal subtype mediated behaviors. Conditional transgenic Rosa26:LSL-dCas9-p300 mice were recently generated to allow for robust expression of dCas9-p300 expression with Cre-driven cell-type specificity. This system utilizes p300, a histone acetyltransferase which regulates gene expression by unwinding chromatin and making that region of the genome more accessible for transcription. Rosa26-LSL-dCas9-p300 mice were paired with Drd1-Cre and Ador2a-Cre mice to generate Drd1-Cre:dCas9-p300 and Ador2a-Cre:dCas9-p300 mouse lines and underwent behavioral phenotyping when sgRNAs were not present. Both Drd1-Cre:dCas9-p300 and Ador2a-Cre:dCas9-p300 have cell-type-specific expression of spCas9 mRNA. Baseline behavioral assessments revealed that, under a sgRNA absent nontargeted state, Drd1-Cre:dCas9-p300 mice display repetitive spinning behavior, hyperlocomotion, and enhanced acquisition of reward learning in comparison with all genotypic littermates. In contrast, Ador2a-Cre:dCas9-p300 do not exhibit any changes in behavior in comparison with their littermates. Electrophysiological recordings of dorsal striatum D1-SPNs revealed that Drd1-Cre:dCas9-p300 mice have increased input resistance and increased spontaneous excitatory postsynaptic current amplitude, together suggesting greater excitatory drive of D1-SPNs. Overall, these data demonstrate the necessity to validate CRISPR-dCas9 lines for research investigations. Additionally, the Drd1-Cre:dCas9-p300 line has the potential to be used to study underlying mechanisms of stereotypy and reward learning.

Indexed as

Behavior, AnimalCorpus StriatumReceptors, Dopamine D1AnimalsCRISPR-Cas SystemsMaleMiceMice, Inbred C57BLMice, TransgenicMotor ActivityRewardDrd1 protein, mouseReceptors, Dopamine D1CRISPR activationepigenome editingnucleus accumbensreward learningstereotypystriatum

Identifiers

PMID40707359
PMCPMC12360625

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.