Transient developmental imbalance of cortical interneuron subtypes presages long-term changes in behavior
Lorenza Magno,
Zeinab Asgarian,
Valentina Pendolino,
Theodora Velona,
Albert Mackintosh,
Flora Lee,
Agata Stryjewska,
Celine Zimmer,
François Guillemot,
Mark Farrant,
Beverley Clark,
Nicoletta Kessaris
Affiliations
Lorenza Magno
Wolfson Institute for Biomedical Research, University College London, Gower Street, London WC1E 6BT, UK; Department of Cell and Developmental Biology, University College London, Gower Street, London WC1E 6BT, UK
Zeinab Asgarian
Wolfson Institute for Biomedical Research, University College London, Gower Street, London WC1E 6BT, UK; Department of Cell and Developmental Biology, University College London, Gower Street, London WC1E 6BT, UK
Valentina Pendolino
Department of Neuroscience, Physiology and Pharmacology, University College London, Gower Street, London WC1E 6BT, UK
Theodora Velona
Wolfson Institute for Biomedical Research, University College London, Gower Street, London WC1E 6BT, UK
Albert Mackintosh
Wolfson Institute for Biomedical Research, University College London, Gower Street, London WC1E 6BT, UK
Flora Lee
Wolfson Institute for Biomedical Research, University College London, Gower Street, London WC1E 6BT, UK
Agata Stryjewska
Wolfson Institute for Biomedical Research, University College London, Gower Street, London WC1E 6BT, UK; Department of Cell and Developmental Biology, University College London, Gower Street, London WC1E 6BT, UK
Celine Zimmer
The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK
François Guillemot
The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK
Mark Farrant
Department of Neuroscience, Physiology and Pharmacology, University College London, Gower Street, London WC1E 6BT, UK
Beverley Clark
Wolfson Institute for Biomedical Research, University College London, Gower Street, London WC1E 6BT, UK; Department of Neuroscience, Physiology and Pharmacology, University College London, Gower Street, London WC1E 6BT, UK
Nicoletta Kessaris
Wolfson Institute for Biomedical Research, University College London, Gower Street, London WC1E 6BT, UK; Department of Cell and Developmental Biology, University College London, Gower Street, London WC1E 6BT, UK; Corresponding author
Summary: Cortical GABAergic interneurons are generated in large numbers in the ganglionic eminences and migrate into the cerebral cortex during embryogenesis. At early postnatal stages, during neuronal circuit maturation, autonomous and activity-dependent mechanisms operate within the cortex to adjust cell numbers by eliminating naturally occurring neuron excess. Here, we show that when cortical interneurons are generated in aberrantly high numbers—due to a defect in precursor cell proliferation during embryogenesis—extra parvalbumin interneurons persist in the postnatal mouse cortex during critical periods of cortical network maturation. Even though cell numbers are subsequently normalized, behavioral abnormalities remain in adulthood. This suggests that timely clearance of excess cortical interneurons is critical for correct functional maturation of circuits that drive adult behavior.
