Evidence map›Paper›PMID 42078876›Full record

ArticleResearch square2026

Aging-related vulnerability in dopamine-glutamate neurons weakens entorhinal dopamine signaling and underlies novelty discrimination deficits.

Jacquelyn N Tomaio, Yifei Li, Omar Ghazy, Gillian H Pavia, Sixtine Fleury, Alexandra Bilder, Jordan Nacimba, Isayana Castillo, William Hilaire, Aaliyah Balogun and 6 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in Research square, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

16 authors.

Jacquelyn N TomaioAdvanced Science Research Center at the Graduate Center, CUNY, New York, NY 10031, USA; Graduate Program in Biology, CUNY Graduate Center, New York, NY 10016, USA.
Yifei LiAdvanced Science Research Center at the Graduate Center, CUNY, New York, NY 10031, USA; Graduate Program in Biology, CUNY Graduate Center, New York, NY 10016, USA.
Omar GhazyAdvanced Science Research Center at the Graduate Center, CUNY, New York, NY 10031, USA; Graduate Program in Biology, CUNY Graduate Center, New York, NY 10016, USA.ORCID 0009-0007-2780-2854
Gillian H PaviaAdvanced Science Research Center at the Graduate Center, CUNY, New York, NY 10031, USA; Graduate Program in Biology, CUNY Graduate Center, New York, NY 10016, USA.
Sixtine FleuryAdvanced Science Research Center at the Graduate Center, CUNY, New York, NY 10031, USA; Graduate Program in Biology, CUNY Graduate Center, New York, NY 10016, USA.
Alexandra BilderAdvanced Science Research Center at the Graduate Center, CUNY, New York, NY 10031, USA; Graduate Program in Biology, CUNY Graduate Center, New York, NY 10016, USA.
Jordan NacimbaAdvanced Science Research Center at the Graduate Center, CUNY, New York, NY 10031, USA; Graduate Program in Biology, CUNY Graduate Center, New York, NY 10016, USA.
Isayana CastilloAdvanced Science Research Center at the Graduate Center, CUNY, New York, NY 10031, USA; Graduate Program in Biology, CUNY Graduate Center, New York, NY 10016, USA.
William HilaireAdvanced Science Research Center at the Graduate Center, CUNY, New York, NY 10031, USA; Graduate Program in Biology, CUNY Graduate Center, New York, NY 10016, USA.
Aaliyah BalogunAdvanced Science Research Center at the Graduate Center, CUNY, New York, NY 10031, USA; Graduate Program in Biology, CUNY Graduate Center, New York, NY 10016, USA.
Lakshman AbhilashAdvanced Science Research Center at the Graduate Center, CUNY, New York, NY 10031, USA; Graduate Program in Biology, CUNY Graduate Center, New York, NY 10016, USA.
Yoon Seok KimDepartment of Bioengineering, Stanford University, Stanford, CA 94305, USA.
Charu RamakrishnanDepartment of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94305, USA; Department of Bioengineering, Stanford University, Stanford, CA 94305, USA; Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA.ORCID 0000-0002-3474-6332
Lief E FennoDepartment of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94305, USA; Department of Bioengineering, Stanford University, Stanford, CA 94305, USA.ORCID 0000-0002-5237-6179
Karl DeisserothDepartment of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94305, USA; Department of Bioengineering, Stanford University, Stanford, CA 94305, USA; Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA.ORCID 0000-0001-9440-3967
Susana MingoteAdvanced Science Research Center at the Graduate Center, CUNY, New York, NY 10031, USA; Graduate Program in Biology, CUNY Graduate Center, New York, NY 10016, USA.ORCID 0000-0002-0401-4317

Funding

Queensborough Community College?s (QCC) Bridges to the Baccalaureate ProgramR25GM065096 · NIGMS · QUEENSBOROUGH COMMUNITY COLLEGE · PI LEVITT, JONATHAN B, SCHNEIDER, PATRICIA · 2002 to 2022
$5.6M
MARC HONORS UNDERGRADUATE RESEARCH TRAINING PROGRAMT34GM007639 · NIGMS · CITY COLLEGE OF NEW YORK · PI LEVITT, JONATHAN B · 1985 to 2022
$4.7M
Dopaminergic Mechanism for Familiarity and Memory InterferenceR21AG085288 · NIA · ADVANCED SCIENCE RESEARCH CENTER · PI PASSOS MINGOTE, SUSANA · 2024 to 2024
$435k
Effects of Decreased Dopamine Synthesis on Glutamate Co-Transmission and Cortical ActivityR21MH123926 · NIMH · ADVANCED SCIENCE RESEARCH CENTER · PI PASSOS MINGOTE, SUSANA · 2021 to 2022
$432k
NIA NIH HHS R21 AG085288NIGMS NIH HHS R25 GM065096NIGMS NIH HHS T34 GM007639NIMH NIH HHS R21 MH123926
6 · The paper itself

Abstract

The lateral entorhinal cortex supports novelty detection and episodic memory and is highly vulnerable to aging. Dopamine conveys novelty signals in this region, but how aging alters this input is unknown. Using viral strategies to distinguish ventral tegmental area dopamine neurons with or without glutamate co-release, we show that co-releasing neurons comprise about 30% of dopamine neurons yet provide nearly all dopaminergic input to the lateral entorhinal cortex. In aged mice, these axons show reduced markers of dopamine synthesis and diminished dopamine release during high-frequency activity, whereas glutamate-related markers are reduced to a lesser extent. Stimulation of lateral entorhinal dopaminergic axons during novelty exploration restores novelty discrimination in aged mice. Together, these findings identify the age-related vulnerability of dopamine-glutamate neurons as a circuit-specific mechanism that impairs entorhinal dopamine signaling and underlies to deficits in novelty discrimination.

Identifiers

PMID42078876
PMCPMC13131891

What OpenQuestion holds

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Registered trials

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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.