Activity-dependent regulation of inhibitory synapse development by Npas4

Yingxi Lin, Brenda L. Bloodgood, Jessica L. Hauser, Ariya D. Lapan, Alex C. Koon, Tae-Kyung Kim, Linda S. Hu, Athar N. Malik and Michael E. Greenberg ()
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Yingxi Lin: F. M. Kirby Neurobiology Center, Harvard Medical School, 300 Longwood Avenue, Boston, Massachusetts 02115, USA
Brenda L. Bloodgood: F. M. Kirby Neurobiology Center, Harvard Medical School, 300 Longwood Avenue, Boston, Massachusetts 02115, USA
Jessica L. Hauser: F. M. Kirby Neurobiology Center, Harvard Medical School, 300 Longwood Avenue, Boston, Massachusetts 02115, USA
Ariya D. Lapan: Program in Biological and Biomedical Sciences, Harvard Medical School, 240 Longwood Avenue, Boston, Massachusetts 02115, USA
Alex C. Koon: F. M. Kirby Neurobiology Center, Harvard Medical School, 300 Longwood Avenue, Boston, Massachusetts 02115, USA
Tae-Kyung Kim: F. M. Kirby Neurobiology Center, Harvard Medical School, 300 Longwood Avenue, Boston, Massachusetts 02115, USA
Linda S. Hu: F. M. Kirby Neurobiology Center, Harvard Medical School, 300 Longwood Avenue, Boston, Massachusetts 02115, USA
Athar N. Malik: F. M. Kirby Neurobiology Center, Harvard Medical School, 300 Longwood Avenue, Boston, Massachusetts 02115, USA
Michael E. Greenberg: F. M. Kirby Neurobiology Center, Harvard Medical School, 300 Longwood Avenue, Boston, Massachusetts 02115, USA

Nature, 2008, vol. 455, issue 7217, 1198-1204

Abstract: Abstract Neuronal activity regulates the development and maturation of excitatory and inhibitory synapses in the mammalian brain. Several recent studies have identified signalling networks within neurons that control excitatory synapse development. However, less is known about the molecular mechanisms that regulate the activity-dependent development of GABA (γ-aminobutyric acid)-releasing inhibitory synapses. Here we report the identification of a transcription factor, Npas4, that plays a role in the development of inhibitory synapses by regulating the expression of activity-dependent genes, which in turn control the number of GABA-releasing synapses that form on excitatory neurons. These findings demonstrate that the activity-dependent gene program regulates inhibitory synapse development, and suggest a new role for this program in controlling the homeostatic balance between synaptic excitation and inhibition.

Date: 2008
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DOI: 10.1038/nature07319

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