Scientific Understanding of Consciousness
Consciousness as an Emergent Property of Thalamocortical Activity

Activity-Dependent Regulation of Inhibitory Synapse Development


Nature 455, 1198-1204 (30 October 2008)

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, Michael E. Greenberg

F. M. Kirby Neurobiology Center, Children's Hospital and Departments of Neurology and Neurobiology, Harvard Medical School, 300 Longwood Avenue, Boston, Massachusetts 02115, USA

Program in Biological and Biomedical Sciences, Harvard Medical School, 240 Longwood Avenue, Boston, Massachusetts 02115, USA

Program in Neuroscience, Harvard Medical School, 300 Longwood Avenue, Boston, Massachusetts 02115, USA

Present addresses: Baylor College of Medicine, Medical Scientist Training Program, One Baylor Plaza Suite N201, MS:BCM215, Houston, Texas 77030-7498, USA (J.L.H.); University of Massachusetts Medical School, Lazare Medical Research Building, Room 760C, 364 Plantation Street, Worcester, Massachusetts 06105, USA (A.C.K.).


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 (gamma-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.

Neurological disorders such as autism, schizophrenia and epilepsy are associated with an imbalance between excitatory and inhibitory synapses.

The density of inhibitory synapses in brain regions such as primary sensory cortex, hippocampus and cerebellum is regulated by the level of excitatory synaptic activity and sensory input.

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