Dual midbrain and forebrain origins of thalamic inhibitory interneurons
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Abstract
The ubiquitous presence of inhibitory interneurons in the thalamus of primates contrasts with the sparsity of interneurons reported in mice. Here, we identify a larger than expected complexity and distribution of interneurons across the mouse thalamus, where all thalamic interneurons can be traced back to two developmental programmes: one specified in the midbrain and the other in the forebrain. Interneurons migrate to functionally distinct thalamocortical nuclei depending on their origin: the abundant, midbrain-derived class populates the first and higher order sensory thalamus while the rarer, forebrain-generated class is restricted to some higher order associative regions. We also observe that markers for the midbrain-born class are abundantly expressed throughout the thalamus of the New World monkey marmoset. These data therefore reveal that, despite the broad variability in interneuron density across mammalian species, the blueprint of the ontogenetic organisation of thalamic interneurons of larger-brained mammals exists and can be studied in mice.
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Glutamatergic subclass 168 SPA-SPFm-SPFp-POL-PIL-PoT Sp9 Glut and GABAergic subclass 203 LGv-SPFp-SPFm Nkx2-2 Tcf7l2 Gaba belong to MB Glut and MB GABA classes, respectively, but they are both located in various posterior thalamic nuclei, suggesting potential migration of these neurons from midbrain pretectal area to thalamus.
“Glutamatergic subclass 168 SPA–SPFm–SPFp–POL–PIL–PoT Sp9 Glut and GABAergic subclass 203 LGv-SPFp-SPFm Nkx2-2 Tcf7l2 Gaba belong to MB Glut and MB GABA classes, respectively, but they are both located in various posterior thalamic nuclei, suggesting potential migration of these neurons from midbrain pretectal area to thalamus40”
From A high-resolution transcriptomic and spatial atlas of cell types in the whole mouse brain (2023) · cites this paper as [40]
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A phylogenetically-conserved axis of thalamocortical connectivity in the human brainPreprint
Oldham, S., & Ball, G. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.11.15.516574
Hierarchical Bayesian modeling of multiregion brain cell count data
Dimmock, S., Exley, B. M., Moore, G., Menage, L., Delogu, A., Schultz, S. R., Warburton, E. C., Houghton, C. J., & O’Donnell, C. (2025) · eLife · doi:10.7554/elife.102391.3
Self-citationSox21 homeologs autoregulate expression levels to control progression through neurogenesis
Damuth, D. L., Cunningham, D. D., & Casey, E. S. (2024) · genesis · doi:10.1002/dvg.23612
Hierarchical Bayesian modeling of multi-region brain cell count dataPreprint
Dimmock, S., Exley, B. M., Moore, G., Menage, L., Delogu, A., Schultz, S. R., Warburton, E. C., Houghton, C. J., & O’Donnell, C. (2024) · eLife · doi:10.7554/elife.102391.1
Self-citationHierarchical Bayesian modeling of multi-region brain cell count dataPreprint
Dimmock, S., Exley, B. M., Moore, G., Menage, L., Delogu, A., Schultz, S. R., Warburton, E. C., Houghton, C. J., & O’Donnell, C. (2025) · eLife · doi:10.7554/elife.102391.2
Self-citationLocal thalamic interneurons drive spindle termination and enable sleep-dependent learningPreprint
Simko, J., Ramirez, T. K., Martin, C., Leung, S., Sung, E. A., & Makinson, C. D. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.09.26.678870
Thalamic Activity Regulates Interneuron Density in the Developing Visual Thalamus
Huerga-Gómez, I., Torres, D., Castellano-Ruiz, P., Wilson, E. S., Martini, F. J., & López‐Bendito, G. (2026) · Journal of Neuroscience · doi:10.1523/jneurosci.0247-25.2026
Spatiotemporal clonal architecture of the newborn mouse forebrain
Yuan, G., Kunst, M., Steyert, M. R., Keefe, M. G., Mathieu, R., van Velthoven, C. T. J., McMillen, D., Waters, J., Fukushima, Y., Kazerounian, A., et al. (2026) · Nature · doi:10.1038/s41586-026-11064-8
- Authors
- Jager, P., Moore, G., Calpin, P., Durmishi, X., Salgarella, I., Menage, L., Kita, Y., Wang, Y., Kim, D. W., Blackshaw, S., Schultz, S. R., Brickley, S., Shimogori, T., & Delogu, A.
- Affiliations
- King's College London (GB)
- Imperial College London (GB)
- University College London (GB)
- RIKEN Center for Brain Science (JP)
- Johns Hopkins University (US)
- Corresponding author
- Delogu, Alessio
- ORCID
- Venue
- eLife
- Publisher
- eLife Sciences Publications, Ltd
- Published
- 2021-02-01
- Volume
- 10
- ISSN
- 2050-084X (ISSN-L)
- PMC
- PMC7906600
- OpenAlex
- W3128622764
- Cited by
- 61
- References
- 134
- Citations by year
- 2026: 6 · 2025: 11 · 2024: 9 · 2023: 16 · 2022: 9 · 2021: 8 · 2020: 1 · 2019: 1
- FWCI
- 3.83
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- eLife (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Research Portal (King's College London) (submittedVersion, cc-by)
- Spiral (Imperial College London) (submittedVersion, cc-by)
- Funders
- Biotechnology and Biological Sciences Research Council (BB/L020068/1, BB/R007020/1, BB/R007659/1)
- Engineering and Physical Sciences Research Council (EP/J021199/1, EP/L016737/1)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- thalamus, interneuron migration, sensory thalamus, marmoset, interneuron density, ontogeny
- MeSH terms
- Animals, Callithrix, Cell Movement, Female, Interneurons, Male, Mesencephalon, Mice, Transgenic, Thalamus, Prosencephalon, In Situ Hybridization, Gene Expression Regulation, Developmental, Cell Lineage, Mice, GABAergic Neurons
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