Cited by 502Epilepsy research and treatmentNeurogenesis and neuroplasticity mechanismsNeuroscience and Neuropharmacology Research

Mice lacking Dlx1 show subtype-specific loss of interneurons, reduced inhibition and epilepsy

Cobos, Inma, Calcagnotto, Maria Elisa, Vilaythong, Alex J, Thwin, Myo T, Noebels, Jeffrey L, Baraban, Scott C, Rubenstein, John L R·2005·Nature Neuroscience

Abstract

Dlx homeodomain transcription factors are essential during embryonic development for the production of forebrain GABAergic interneurons. Here we show that Dlx1 is also required for regulating the functional longevity of cortical and hippocampal interneurons in the adult brain. We demonstrate preferential Dlx1 expression in a subset of cortical and hippocampal interneurons which, in postnatal Dlx1 mutants, show a time-dependent reduction in number. This reduction preferentially affects calretinin(+) (bipolar cells) and somatostatin(+) subtypes (for example, bitufted cells), whereas parvalbumin(+) subpopulations (basket cells and chandelier cells) seem to be unaffected. Cell transplantation analysis demonstrates that interneuron loss reflects cell-autonomous functions of Dlx1. The decrease in the number of interneurons was associated with a reduction of GABA-mediated inhibitory postsynaptic current in neocortex and hippocampus in vitro and cortical dysrhythmia in vivo. Dlx1 mutant mice show generalized electrographic seizures and histological evidence of seizure-induced reorganization, linking the Dlx1 mutation to delayed-onset epilepsy associated with interneuron loss.

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Crossref · 10.1038/nn1499

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  • Dlx1 is critically required for maturation of some classes of cortical interneurons.

    “a transcription factor that is critically required for the maturation of some classes of cortical interneurons (Cobos et al., 2005)”

    From Development and Functional Diversification of Cortical Interneurons (2018) · cites this paper as Cobos et al., 2005

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Authors
Cobos, I., Calcagnotto, M. E., Vilaythong, A. J., Thwin, M. T., Noebels, J. L., Baraban, S. C., & Rubenstein, J. L. R.
Affiliations
  • University of California, San Francisco (US)
  • Baylor College of Medicine (US)
Corresponding author
  • Cobos, Inma
  • Rubenstein, John L R
Venue
Nature Neuroscience
Published
2005-07-10
Volume
8
Issue
8
Pages
1059-1068
ISSN
  • 1097-6256 (ISSN-L)
  • 1546-1726
OpenAlex
W2005402594
Cited by
502
References
50
Citations by year
2026: 8 · 2025: 10 · 2024: 15 · 2023: 15 · 2022: 20 · 2021: 17 · 2020: 14 · 2019: 20 · 2018: 25 · 2017: 28 · 2016: 16 · 2015: 23 · 2014: 30 · 2013: 38 · 2012: 31
FWCI
15.31
Type
journal article
Language
en
Open access
closed
Locations
  • Nature Neuroscience (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institute of Mental Health (R01MH49428, K05MH065670, R01MH049428)
  • National Institute of Neurological Disorders and Stroke (R01 NS40272, R01NS040272, NS29709, R01NS029709)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD 24064, P30HD024064)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
DLX1, GABAergic interneurons, interneuron loss, calretinin, somatostatin, parvalbumin, inhibitory postsynaptic currents, cell-autonomous function, cell transplantation, hippocampus, neocortex
MeSH terms
Aging, Animals, Behavior, Animal, Brain, Cell Count, Cerebral Cortex, Epilepsy, gamma-Aminobutyric Acid, Interneurons, Neural Inhibition, Neurons, Synapses, Transcription Factors, Apoptosis, Gene Deletion, Mice, Knockout, Homeodomain Proteins, Mice

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