The fraction of cortical GABAergic neurons is constant from near the start of cortical neurogenesis to adulthood
Open accessAbstract
Approximately one in five neurons is GABAergic in many neocortical areas and species, forming a critical balance between inhibition and excitation in adult circuits. During development, cortical GABAergic neurons are generated in ventral telencephalon and migrate up to developing cortex where the excitatory glutamatergic neurons are born. We ask here: when during development is the adult GABAergic/glutamatergic neuron ratio first established? To answer this question, we have determined the fraction of all neocortical GABAergic neurons that will become inhibitory (GAD67(+)) in mice from embryonic day 10.5 (E10.5) to postnatal day 28 (P28). We find that this fraction is close to 1/5, the adult value, starting from early in corticogenesis (E14.5, when GAD67(+) neurons are still migrating tangentially to the cortex) and continuing at the same 1/5 value throughout the remainder of brain development. Thus our data indicate the one-in-five fraction of GABAergic neurons is already established during their neuronal migration and well before significant synapse formation.
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
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?
The sampled neuron population is roughly half GABAergic (47%) and half glutamatergic (53%) due to enrichment by design.
“This enrichment procedure resulted, by design, in a disproportionate representation of GABAergic neurons, canonically ~20% of neurons (Sahara et al., 2012), such that the sampled neuron population is roughly half GABAergic (47%) and half glutamatergic (53%).”
From Single-cell transcriptomic evidence for dense intracortical neuropeptide networks (2019) · cites this paper as Sahara et al., 2012
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
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 · see citing works
Excitatory actions of gaba during development: the nature of the nurture
Ben-Ari, Y. (2002) · Nature Reviews Neuroscience · doi:10.1038/nrn920 · Cited by 2,448 · see citing works
NeuN, a neuronal specific nuclear protein in vertebratesxs
Mullen, R. J., Buck, C. R., & Smith, A. M. (1992) · Development · doi:10.1242/dev.116.1.201 · Cited by 2,351 · see citing works
Petilla terminology: nomenclature of features of GABAergic interneurons of the cerebral cortex
The Petilla Interneuron Nomenclature Group (PING) (2008) · Nature Reviews Neuroscience · doi:10.1038/nrn2402 · Cited by 1,491 · see citing works
Interneuron Migration from Basal Forebrain to Neocortex: Dependence on <i>Dlx</i> Genes
Anderson, S. A., Eisenstat, D. D., Shi, L., & Rubenstein, J. L. R. (1997) · Science · doi:10.1126/science.278.5337.474 · Cited by 1,462 · see citing works
Regressive Events in Neurogenesis
Cowan, W. M., Fawcett, J. W., O'Leary, D. D. M., & Stanfield, B. B. (1984) · Science · doi:10.1126/science.6474175 · Cited by 1,316 · see citing works
Self-citationTamamaki, N., Yanagawa, Y., Tomioka, R., Miyazaki, J., Obata, K., & Kaneko, T. (2003) · The Journal of Comparative Neurology · doi:10.1002/cne.10905 · Cited by 1,277 · see citing works
Self-citationLavdas, A. A., Grigoriou, M., Pachnis, V., & Parnavelas, J. G. (1999) · The Journal of Neuroscience · doi:10.1523/jneurosci.19-18-07881.1999 · Cited by 765 · see citing works
Ganguly, K., Schinder, A. F., Wong, S. T., & Poo, M. (2001) · Cell · doi:10.1016/s0092-8674(01)00341-5 · Cited by 719 · see citing works
Patterns of neuronal migration in the embryonic cortex
Kriegstein, A. R., & Noctor, S. C. (2004) · Trends in Neurosciences · doi:10.1016/j.tins.2004.05.001 · Cited by 648 · see citing works
Origins of Cortical Interneuron Subtypes
Xu, Q., Cobos, I., De La Cruz, E., Rubenstein, J. L., & Anderson, S. A. (2004) · The Journal of Neuroscience · doi:10.1523/jneurosci.5667-03.2004 · Cited by 639 · see citing works
Esclapez, M., Tillakaratne, N. J. K., Kaufman, D. L., Tobin, A., & Houser, C. R. (1994) · Journal of Neuroscience · doi:10.1523/jneurosci.14-03-01834.1994 · Cited by 614 · see citing works
Numbers and proportions of GABA-immunoreactive neurons in different areas of monkey cerebral cortex
Hendry, S., Schwark, H. D., Jones, E. G., & Yan, J. (1987) · Journal of Neuroscience · doi:10.1523/jneurosci.07-05-01503.1987 · Cited by 601 · see citing works
Area Patterning of the Mammalian Cortex
O’Leary, D. D. M., Chou, S., & Sahara, S. (2007) · Neuron · doi:10.1016/j.neuron.2007.10.010 · Cited by 574 · see citing works
Self-citationThe caudal ganglionic eminence is a source of distinct cortical and subcortical cell populations
Nery, S., Fishell, G., & Corbin, J. G. (2002) · Nature Neuroscience · doi:10.1038/nn971 · Cited by 558 · see citing works
Menezes, J., & Luskin, M. (1994) · Journal of Neuroscience · doi:10.1523/jneurosci.14-09-05399.1994 · Cited by 469 · see citing works
Mechanisms of programmed cell death in the developing brain
Kuan, C.-Y., Roth, K. A., Flavell, R. A., & RAKIC, P. T. (2000) · Trends in Neurosciences · doi:10.1016/s0166-2236(00)01581-2 · Cited by 444 · see citing works
Short- and long-range attraction of cortical GABAergic interneurons by neuregulin-1
Flames, N., Long, J. E., Garratt, A. N., Fischer, T. M., Gassmann, M., Birchmeier, C., Lai, C., Rubenstein, J. L. R., & Marı́n, O. (2004) · Neuron · doi:10.1016/j.neuron.2004.09.028 · Cited by 431 · see citing works
Guiding Neuronal Cell Migrations
Marin, O., Valiente, M., Ge, X., & Tsai, L.-H. (2010) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a001834 · Cited by 417 · see citing works
Bortone, D., & Polleux, F. (2009) · Neuron · doi:10.1016/j.neuron.2009.01.034 · Cited by 387 · see citing works
Single-Synapse Analysis of a Diverse Synapse Population: Proteomic Imaging Methods and Markers
Micheva, K. D., Busse, B. L., Weiler, N. C., O’Rourke, N. A., & Smith, S. J. (2010) · Neuron · doi:10.1016/j.neuron.2010.09.024 · Cited by 336 · see citing works
Neuronal activity is required for the development of specific cortical interneuron subtypes
De Marco García, N. V., Karayannis, T., & Fishell, G. (2011) · Nature · doi:10.1038/nature09865 · Cited by 294 · see citing works
Cell Lineages and the Logic of Proliferative Control
Lander, A. D., Gokoffski, K. K., Wan, F. Y. M., Nie, Q. H., & Calof, A. L. (2009) · PLoS Biology · doi:10.1371/journal.pbio.1000015 · Cited by 289 · see citing works
Four-Dimensional Migratory Coordinates of GABAergic Interneurons in the Developing Mouse Cortex
Ang, E. S. B. C., Haydar, T. F., Gluncic, V., & Rakic, P. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-13-05805.2003 · Cited by 282 · see citing works
Development of GABA innervation in the cerebral and cerebellar cortices
Huang, Z. J., Cristo, G. D., & Ango, F. (2007) · Nature reviews. Neuroscience · doi:10.1038/nrn2188 · Cited by 281 · see citing works
Cortical Plasticity Induced by Inhibitory Neuron Transplantation
Southwell, D. G., Froemke, R. C., Alvarez-Buylla, A., Stryker, M. P., & Gandhi, S. P. (2010) · Science · doi:10.1126/science.1183962 · Cited by 271 · see citing works
Esclapez, M., Tillakaratne, N. J. K., Tobin, A. J., & Houser, C. R. (1993) · The Journal of Comparative Neurology · doi:10.1002/cne.903310305 · Cited by 251 · see citing works
Lodato, S., Rouaux, C., Quast, K. B., Jantrachotechatchawan, C., Studer, M., Hensch, T. K., & Arlotta, P. (2011) · Neuron · doi:10.1016/j.neuron.2011.01.015 · Cited by 244 · see citing works
López-Bendito, G., Sánchez-Alcañiz, J. A., Pla, R., Borrell, V., Picó, E., Valdeolmillos, M., & Marín, O. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.4651-07.2008 · Cited by 236 · see citing works
Ventricle-directed migration in the developing cerebral cortex
Nadarajah, B., Alifragis, P., Wong, R., & Parnavelas, J. G. (2002) · Nature Neuroscience · doi:10.1038/nn813 · Cited by 219 · see citing works
Sahara, S., & O’Leary, D. D. M. (2009) · Neuron · doi:10.1016/j.neuron.2009.06.006 · Cited by 206 · see citing works
Self-citationLayer Specification of Transplanted Interneurons in Developing Mouse Neocortex
Valcanis, H., & Tan, S.-S. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-12-05113.2003 · Cited by 175 · see citing works
Fairén, A., Cobas, A., & Fonseca, M. (1986) · Journal of Comparative Neurology · doi:10.1002/cne.902510105 · Cited by 158 · see citing works
Expression of the Class III β‐tubulin isotype in developing neurons in culture
Ferreira, A., & Cáceres, A. (1992) · Journal of Neuroscience Research · doi:10.1002/jnr.490320407 · Cited by 136 · see citing works
Tanaka, D. H., Maekawa, K., Yanagawa, Y., Obata, K., & Murakami, F. (2006) · Development · doi:10.1242/dev.02382 · Cited by 128 · see citing works
Self-citationShinozaki, K., Miyagi, T., Yoshida, M., Miyata, T., Ogawa, M., Aizawa, S., & Suda, Y. (2002) · Development · doi:10.1242/dev.129.14.3479 · Cited by 128 · see citing works
Laminar fate of cortical GABAergic interneurons is dependent on both birthdate and phenotype
Rymar, V. V., & Sadikot, A. F. (2007) · The Journal of Comparative Neurology · doi:10.1002/cne.21250 · Cited by 116 · see citing works
Carlson, V. C. C., Yeh, P. W. L., Cheng, Q., & Yeh, H. H. (2005) · Cerebral Cortex · doi:10.1093/cercor/bhj084 · Cited by 109 · see citing works
Cavanagh, M. E., & Parnavelas, J. G. (1988) · The Journal of Comparative Neurology · doi:10.1002/cne.902680102 · Cited by 107 · see citing works
Ferreira, A., Busciglio, J. A., & Cáceres, A. (1987) · Developmental Brain Research · doi:10.1016/0165-3806(87)90191-x · Cited by 86 · see citing works
Li, H., Chou, S., Hamasaki, T., Pérez‐García, C. G., & O’Leary, D. D. M. (2012) · Neural Development · doi:10.1186/1749-8104-7-10 · Cited by 57 · see citing works
Self-citationYozu, M., Tabata, H., & Nakajima, K. (2004) · Neuroscience Research · doi:10.1016/j.neures.2004.05.005 · Cited by 46 · see citing works
Commentary: The Prospect of Cell-Based Therapy for Epilepsy
Kriegstein, A. R., & Pitkänen, A. (2009) · Neurotherapeutics · doi:10.1016/j.nurt.2009.01.013 · Cited by 7 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Nagy, C., Maitra, M., Tanti, A., Suderman, M., Théroux, J.-F., Davoli, M. A., Perlman, K., Yerko, V., Wang, Y. C., Tripathy, S. J., et al. (2020) · Nature Neuroscience · doi:10.1038/s41593-020-0621-y · Cited by 532 · see citing works
Intrinsically determined cell death of developing cortical interneurons
Southwell, D. G., Paredes, M. F., Galvao, R. P., Jones, D. L., Froemke, R. C., Sebe, J. Y., Alfaro-Cervello, C., Tang, Y., Garcia-Verdugo, J. M., Rubenstein, J. L., et al. (2012) · Nature · doi:10.1038/nature11523 · Cited by 365 · see citing works
Parvalbumin interneuron vulnerability and brain disorders
Ruden, J. B., Dugan, L. L., & Konradi, C. (2021) · Neuropsychopharmacology · doi:10.1038/s41386-020-0778-9 · Cited by 194 · see citing works
Integration of GABAergic interneurons into cortical cell assemblies: lessons from embryos and adults
Bartolini, G., Ciceri, G., & Marín, O. (2013) · Neuron · doi:10.1016/j.neuron.2013.08.014 · Cited by 185 · see citing works
Single-cell transcriptomic evidence for dense intracortical neuropeptide networks
Smith, S. J., Sümbül, U., Graybuck, L. T., Collman, F., Seshamani, S., Gala, R., Gliko, O., Elabbady, L., Miller, J. A., Bakken, T. E., et al. (2019) · eLife · doi:10.7554/elife.47889 · Cited by 156 · see citing works
Blanquie, O., Yang, J.-W., Kilb, W., Sharopov, S., Sinning, A., & Luhmann, H. J. (2017) · eLife · doi:10.7554/elife.27696 · Cited by 114 · see citing works
Neuronal circuits overcome imbalance in excitation and inhibition by adjusting connection numbers
Sukenik, N., Vinogradov, O., Weinreb, E., Segal, M., Levina, A., & Moses, E. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2018459118 · Cited by 109 · see citing works
GABAergic Restriction of Network Dynamics Regulates Interneuron Survival in the Developing Cortex
Duan, Z. R. S., Che, A., Chu, P., Modol, L., Bollmann, Y., Babij, R., Fetcho, R. N., Otsuka, T., Fuccillo, M. V., Liston, C., et al. (2020) · Neuron · doi:10.1016/j.neuron.2019.10.008 · Cited by 102 · see citing works
Onwordi, E. C., Whitehurst, T., Mansur, A., Statton, B., Berry, A., Quinlan, M., O’Regan, D. P., Rogdaki, M., Marques, T. R., Rabiner, E. A., et al. (2021) · Translational Psychiatry · doi:10.1038/s41398-021-01515-3 · Cited by 55 · see citing works
Vandenberg, A., Piekarski, D. J., Caporale, N., Munoz-Cuevas, F. J., & Wilbrecht, L. (2015) · Frontiers in Neural Circuits · doi:10.3389/fncir.2015.00005 · Cited by 22 · see citing works
- Authors
- Sahara, S., Yanagawa, Y., O'Leary, D. D. M., & Stevens, C. F.
- Affiliations
- Salk Institute for Biological Studies (US)
- Gunma University (JP)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2012-04-04
- Volume
- 32
- Issue
- 14
- Pages
- 4755-4761
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC3325497
- OpenAlex
- W2073248815
- Cited by
- 198
- References
- 43
- Citations by year
- 2026: 8 · 2025: 21 · 2024: 24 · 2023: 19 · 2022: 14 · 2021: 15 · 2020: 16 · 2019: 15 · 2018: 19 · 2017: 15 · 2016: 3 · 2015: 6 · 2014: 9 · 2013: 8 · 2012: 5
- FWCI
- 2.99
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (King's College London) (submittedVersion)
- Funders
- National Institute of Mental Health (R01MH086147)
- National Institute of Neurological Disorders and Stroke (R01NS031558, R37NS031558)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- GABAergic neurons, cortical neurogenesis, GAD67, neuronal migration, tangential migration, ventral telencephalon, neocortex development, inhibitory interneurons, synaptogenesis
- MeSH terms
- Aging, Animals, Animals, Newborn, Cell Movement, Cerebral Cortex, Female, Glutamate Decarboxylase, Male, Mice, Inbred ICR, Pregnancy, Random Allocation, Mice, Neurogenesis, Gene Knock-In Techniques, GABAergic Neurons
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