EBD Blog

Neurons in the central nervous system communicate with each other chemically through neural synapses. Neurons receive excitatory input from glutamatergic neurons and inhibitory input from GABA-releasing (GABAergic) interneurons. Some hypotheses about Autism are predicated on the possibility that there is an imbalance between the excitatory and inhibitory neural activity, perhaps especially in the so-called mirror neurons. Reporting in Nature, Yingxi Lin and fellow scientistics working in Michael Greenberg’s group at Harvard University have discovered a gene—Npas4—that may regulate the balance between excessive and insufficient excitation of synapses.

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 (-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.

Nature , | doi:10.1038/nature07319; Received 5 May 2008; Accepted 25 July 2008; Published online 24 September 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

Although there are other potential genetic factors implicated in Autism and schizophrenia, this discovery may help close the gap between fundamental science about correlated differences and mechanisms for affecting the performance of the individuals who have the disorder.

1. Link to the original article in Nature;
2. Coverage of the story from Scientific American;
3. Link to the Web site for Professor Greenberg’s lab;
4. More from EBD Blog about mirror neurons: Austism and understanding emotions (Dec 2006), More mirrors on Autism (Jan 2007), and More about mirror neurons (Nov 2007).