The DOI matches its Crossref record; 52 of the 52 references it cites were found in a registry or an index.
Npas4 Regulates Excitatory-Inhibitory Balance within Neural Circuits through Cell-Type-Specific Gene Programs
Open accessAbstract
The nervous system adapts to experience by inducing a transcriptional program that controls important aspects of synaptic plasticity. Although the molecular mechanisms of experience-dependent plasticity are well characterized in excitatory neurons, the mechanisms that regulate this process in inhibitory neurons are only poorly understood. Here, we describe a transcriptional program that is induced by neuronal activity in inhibitory neurons. We find that, while neuronal activity induces expression of early-response transcription factors such as Npas4 in both excitatory and inhibitory neurons, Npas4 activates distinct programs of late-response genes in inhibitory and excitatory neurons. These late-response genes differentially regulate synaptic input to these two types of neurons, promoting inhibition onto excitatory neurons while inducing excitation onto inhibitory neurons. These findings suggest that the functional outcomes of activity-induced transcriptional responses are adapted in a cell-type-specific manner to achieve a circuit-wide homeostatic response.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Npas4 regulates excitatory synapse formation through the induction of a transcriptional program in SST+ interneurons that involves the expression of several synaptic scaffolding proteins and the shaker-like potassium channel Kv1.1 (Spiegel et al., 2014).”
From Development and Functional Diversification of Cortical Interneurons (2018) · cites this paper as Spiegel et al., 2014
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT Method
Livak, K. J., & Schmittgen, T. D. (2001) · Methods · doi:10.1006/meth.2001.1262 · Cited by 180,860
Bolstad, B. M., Irizarry, R. A., Åstrand, M., & Speed, T. P. (2003) · Bioinformatics · doi:10.1093/bioinformatics/19.2.185 · Cited by 8,328
A robust and high-throughput Cre reporting and characterization system for the whole mouse brain
Madisen, L., Zwingman, T. A., Sunkin, S. M., Oh, S. W., Zariwala, H. A., Gu, H., Ng, L. L., Palmiter, R. D., Hawrylycz, M. J., Jones, A. R., et al. (2010) · Nature Neuroscience · doi:10.1038/nn.2467 · Cited by 6,907
Histone H3K27ac separates active from poised enhancers and predicts developmental state
Creyghton, M. P., Cheng, A. W., Welstead, G. G., Kooistra, T., Carey, B. W., Steine, E. J., Hanna, J., Lodato, M. A., Frampton, G. M., Sharp, P. A., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1016071107 · Cited by 4,302
Master Transcription Factors and Mediator Establish Super-Enhancers at Key Cell Identity Genes
Whyte, W. A., Orlando, D. A., Hnisz, D., Abraham, B. J., Lin, C. Y., Kagey, M. H., Rahl, P. B., Lee, T. I., & Young, R. A. (2013) · Cell · doi:10.1016/j.cell.2013.03.035 · Cited by 4,143
Interneurons of the neocortical inhibitory system
Markram, H., Toledo-Rodriguez, M., Wang, Y., Gupta, A., Silberberg, G., & Wu, C. (2004) · Nature Reviews Neuroscience · doi:10.1038/nrn1519 · Cited by 2,954 · cited 3×
“Balance within Neural Circuits through”
SINGLE-CELL RESPONSES IN STRIATE CORTEX OF KITTENS DEPRIVED OF VISION IN ONE EYE
Wiesel, T. N., & Hubel, D. H. (1963) · Journal of Neurophysiology · doi:10.1152/jn.1963.26.6.1003 · Cited by 2,628 · cited 2×
“Balance within Neural Circuits through”
Widespread transcription at neuronal activity-regulated enhancers
Kim, T.-K., Hemberg, M., Gray, J. M., Costa, A. M., Bear, D. M., Wu, J., Harmin, D. A., Laptewicz, M., Barbara-Haley, K., Kuersten, S., et al. (2010) · Nature · doi:10.1038/nature09033 · Cited by 2,450 · cited 2×
“ChIP-seq data sets (Kim et al., 2010) generated from mixed cortical cultures containing both excitatory and inhibitory neurons using anti-Npas4, -CBP, -H3K4me1, and -H3K4me3 antibodies revealed that most Npas4-regulated genes are located near candidate regulatory elements (6 out of 9 genes regulated by Npas4 in MGE on…”
Self-citationCritical period plasticity in local cortical circuits
Hensch, T. K. (2005) · Nature Reviews Neuroscience · doi:10.1038/nrn1787 · Cited by 2,323 · cited 2×
“Balance within Neural Circuits through”
Cortical inhibitory neurons and schizophrenia
Lewis, D. A., Hashimoto, T., & Volk, D. W. (2005) · Nature Reviews Neuroscience · doi:10.1038/nrn1648 · Cited by 2,297 · cited 2×
“Balance within Neural Circuits through”
Flagged first, then by citations
Cited by
Sorted by citations
Items 401–415 of 415
2P-NucTag: On-demand phototagging for molecular analysis of functionally identified cortical neurons
Shi, J., Nutkovich, B., Kushinsky, D., Rao, B. Y., Herrlinger, S. A., Tsivourakis, E., Mihaila, T. S., Paredes, M. E. C., Malina, K. C.-K., O’Toole, C. K., et al. (2026) · Neuron · doi:10.1016/j.neuron.2026.03.016 · Cited by 1
“Genes for which expression has been shown to vary along the dorsoventral and proximodistal axes of CA1 were not differentially expressed in our place and silent-cell nuclei (fig.”
Role of the gut-brain axis in early stress-induced emotional vulnerability
Rincel, M. (2017) · theses.fr (ABES) · doi:10.70675/5e8a972cz9ad1z42aezb89cze6474124ef90
Mao, F., Yang, Y., Jiang, Z., Le, Q., & Jin, T. (2026) · Neuroreport · doi:10.1097/wnr.0000000000002272
Lee, Y.-H., Kuo, H., Chen, S.-Y., Chang, Y.-N., Gerfen, C. R., & Liu, F. (2026) · Molecular Brain · doi:10.1186/s13041-026-01316-z
“Function-ally, Npas4 plays an indispensable role in homeostatic plasticity by orchestrating gene programs that regulate the balance of excitatory and inhibitory (E/I) synaptic connections onto activated neurons [31, 33].”
Gui, Y., Chen, Y., Guo, Q., Luo, Y., Yang, F., Mahaman, Y. A. R., Wang, J.-Z., Liu, R., Luo, H., Shu, X., et al. (2026) · Translational Psychiatry · doi:10.1038/s41398-026-03949-z
Maio, B., Singh, A., Hector, R., Gadalla, K. K. E., Selfridge, J., Aria, F., Louros, S. R., Cobb, S., & Osterweil, E. K. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.06.12.731901
Kashiwagi, Y., Liu, Q., Go, Y., Saito, R., Aiba, A., Nakazawa, T., & Okabe, S. (2026) · eLife · doi:10.7554/elife.109083.2
Námešná, A., Pickford, J., Hall, J., van den Bree, M. B. M., Tait, L., Wilkinson, L. S., & Jones, M. W. (2026) · Genes · doi:10.3390/genes17060716
“This is executed primarily via coordination of inhibitory synapse development, wherein Npas4 promotes the formation and stabilization of inhibitory input onto excitatory neurons and excitatory input onto inhibitory neurons [171,172].”
Kashiwagi, Y., Liu, Q., Go, Y., Saito, R., Aiba, A., Nakazawa, T., & Okabe, S. (2026) · eLife · doi:10.7554/elife.109083.3
Pyne, I. T., Roy, A. J., Boraschi, S., Hajgude, S. S., & Hall, R. A. (2026) · Molecular Pharmacology · doi:10.1016/j.molpha.2026.100146
Cocaine Hijacks the Npas4-dependent Somatostatin Ensembles in the mPFC to Mediate Attention
Hou, X., Han, K., Wang, F., Jiang, C., Ma, L., & Jin, T. (2026) · Neuroscience Bulletin · doi:10.1007/s12264-026-01689-0
Cheng, C., Gao, D., Shen, Y., Wang, X., Dai, J., Xiang, Y., Jiang, Z., You, Z., & Jiang, J. (2026) · CNS Neuroscience & Therapeutics · doi:10.1002/cns.71090
“It promotes the formation of inhibitory synapses and regulates excitatory-inhibitory (E/I) balance in cortical circuits, thereby shaping experience-dependent plasticity [25, 26].”
Interneurons and network activity in the cerebral cortex: a developmental dialogue
Moissidis, M., & Marín, Ó. (2026) · Nature reviews. Neuroscience · doi:10.1038/s41583-026-01088-4
Metadata
- Authors
- Spiegel, I., Mardinly, A. R., Gabel, H. W., Bazinet, J. E., Couch, C. H., Tzeng, C. P., Harmin, D. A., & Greenberg, M. E.
- Affiliations
- Harvard University (US)
- Corresponding author
- Greenberg, Michael E.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2014-05
- Volume
- 157
- Issue
- 5
- Pages
- 1216-1229
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC4089405
- OpenAlex
- W2079540311
- Cited by
- 416
- References
- 52
- Citations by year
- 2026: 31 · 2025: 49 · 2024: 41 · 2023: 28 · 2022: 38 · 2021: 37 · 2020: 29 · 2019: 34 · 2018: 31 · 2017: 32 · 2016: 34 · 2015: 23 · 2014: 8
- FWCI
- 14.77
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (5r01ns048276-15)
- National Institute of Mental Health (T32MH020017)
- National Institute of Neurological Disorders and Stroke (R01NS028829, NS048276, R37NS028829)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (P30HD018655)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- Npas4, excitation-inhibition balance, inhibitory neurons, excitatory neurons, activity-dependent transcription, synaptic plasticity, homeostatic regulation, neural circuits
- MeSH terms
- Animals, Embryo, Mammalian, Gene Expression Regulation, Neurons, Synapses, Transcription, Genetic, Mice, Knockout, Cell Culture Techniques, Mice, Basic Helix-Loop-Helix Proteins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
