Evidence map›Paper›PMID 25757474›Full record

ArticleMolecular brain2015

Ontogeny of biochemical, morphological and functional parameters of synaptogenesis in primary cultures of rat hippocampal and cortical neurons.

Joshua A Harrill, Hao Chen, Karin M Streifel, Dongren Yang, William R Mundy, Pamela J Lein

Open access · goldAbstract read
In one paragraph

Article in Molecular brain, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
3.1field-weighted citation impact, top 8% 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

31 citing papers in PubMed, 56 citations in OpenAlex.

  1. Article
  2. Article
  3. The tyrosine phosphatase STEP is a developmental suppressor of synaptogenesis.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  4. Review
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  6. Mental Health Across the Metabolic Spectrum.Biological psychiatry global open science · 2025
    Review
  7. Volatile oil ofFrontiers in pharmacology · 2025
    Review
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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

6 authors at 2 institutions in 1 country.

Joshua A Harrill
Hao Chen
Karin M Streifel
Dongren Yang
William R Mundy
Pamela J Lein
University of California, Davis · USResearch Triangle Park Foundation · US

Funding

UC Davis Center for Children's Environmental Health (CCEH)P01ES011269 · NIEHS · UNIVERSITY OF CALIFORNIA DAVIS · PI VAN DE WATER, JUDY A. · 2001 to 2018
$12.5M
Molecular and Cellular Basis of PCB Developmental Neurotoxicity: ViCTER supplementR01ES014901 · NIEHS · UNIVERSITY OF CALIFORNIA AT DAVIS · PI HANS-JOACHIM LEHMLER, Pamela J Lein · 2009 to 2026
$9.3M
Rodent Behavior CoreU54HD079125 · NICHD · UNIVERSITY OF CALIFORNIA AT DAVIS · PI SIMON, TONY J · 2013 to 2019
$8.5M
ENVIRONMENTAL TOXICOLOGYT32ES007059 · NIEHS · UNIVERSITY OF CALIFORNIA DAVIS · PI Laura S Van Winkle · 1985 to 2026
$7.9M
Interdisciplinary Training for Autism Researchers(RMI)T32MH073124 · NIMH · UNIVERSITY OF CALIFORNIA DAVIS · PI Stephen Charles Noctor, Christine Wu Nordahl · 2004 to 2026
$6.8M
Organophosphorus pesticides interact with ASD-linked neuroligins to alter synaptoF32ES024676 · NIEHS · UNIVERSITY OF CALIFORNIA AT DAVIS · PI STREIFEL, KARIN MARIE · 2014 to 2014
$55k
NICHD NIH HHS U54 HD079125NIEHS NIH HHS ES011269NIEHS NIH HHS F32 ES024676NIEHS NIH HHS P01 ES011269NIEHS NIH HHS R01 ES014901NIEHS NIH HHS T32 ES007059NIMH NIH HHS T32 MH073124NIMH NIH HHS T32-MH073124
6 · The paper itself

Abstract

backgroundSynaptogenesis is a critical neurodevelopmental process whereby pre- and postsynaptic neurons form apposed sites of contact specialized for chemical neurotransmission. Many neurodevelopmental disorders are thought to reflect altered patterns of synaptic connectivity, including imbalances between excitatory and inhibitory synapses. Developing rapid throughput approaches for assessing synaptogenesis will facilitate toxicologic and drug screening studies of neurodevelopmental disorders. The current study describes the use of high-content imaging to quantify the ontogeny of excitatory and inhibitory synapses using in vitro models of neurodevelopment. These data are compared to biochemical and functional measures of synaptogenesis.

resultsThe ontogenetic patterns of synapse formation were compared between primary rodent hippocampal and cortical neurons over 28 days in vitro (DIV). As determined by ELISA, the increase in synaptophysin expression levels as cultures matured was similar between hippocampal and cortical cultures. High-content imaging of immunoreactivity of excitatory and inhibitory synaptic biomarkers demonstrated an overall greater number of synapses in hippocampal relative to cortical neurons with marked differences in the pattern of inhibitory synapse development between these two neuronal cell types. Functional assays revealed that both the mean firing rates and mean bursting rates were significantly increased in cortical cultures relative to hippocampal cultures. This difference may reflect decreased inhibitory synaptic tone in cortical versus hippocampal cultures.

conclusionsThese data demonstrate differences and similarities in the ontogeny of synaptogenesis between hippocampal and cortical neurons, depending on the biological level examined. Assessment of synaptophysin protein levels by ELISA showed a general increase in synapse formation in both cell types with increasing time in culture, while high-content imaging was able to delineate cell type-dependent differences in formation of excitatory versus inhibitory synapses. The functional significance of differences in the balance of excitatory to inhibitory synapses was confirmed by the assessment of network activity using microelectrode arrays. These results suggest that high-content imaging and microelectrode arrays provide complementary approaches for quantitative assessment of synaptogenesis, which should provide a robust readout of toxicologic and pharmacologic effects on this critical neurodevelopmental event.

Indexed as

NeurogenesisAlgorithmsAnimalsCell CountCells, CulturedCerebral CortexDendritesEnzyme-Linked Immunosorbent AssayFemaleHippocampusMicroelectrodesNerve NetNeural InhibitionNeuronsRats, Sprague-DawleySynapsesSynaptophysin

Identifiers

PMID25757474
PMCPMC4339650
OpenAlexW1977194031

What OpenQuestion holds

Textmetadata
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.