Balancing the Brain


 
1.3k
Shares
 

 

Factor spurring formation of inhibitory synapses gives clues to neurologic disorders

Neuroscientists at Children's Hospital Boston have identified the first known "master switch" in brain cells to orchestrate the formation and maintenance of inhibitory synapses, essential for proper brain function. The factor, called Npas4, regulates more than 200 genes that act in various ways to calm down over-excited cells, restoring a balance that is thought to go askew in some neurologic disorders

Synapses, the connections between brain cells, can be excitatory or inhibitory in nature. At birth, the rapidly developing brain teems with excitatory synapses, which tend to make nerve cells "fire" and stimulate their neighbors. But if the excitation isn't eventually balanced, it can lead to epilepsy, and diseases like autism and schizophrenia have been associated with an imbalance of excitation and inhibition. The creation of inhibitory connections is also necessary to launch critical periods -- windows of rapid learning during early childhood and adolescence, when the brain is very "plastic" and able to rewire itself.

Npas4 is a transcription factor, a switch that activates or represses other genes. The researchers, led by Michael Greenberg, PhD, director of the Neurobiology Program at Children's, demonstrated that the activity of as many as 270 genes changes when Npas4 activity is blocked in a cell, and that Npas4 activation is associated with an increased number of inhibitory synapses on the cell's surface.

The team further showed that Npas4 is activated by excitatory synaptic activity. "Excitation turns on a program that says, 'this cell is getting excited, we need to balance that with inhibition,'" explains Greenberg, who now also chairs the Department of Neurobiology at Harvard Medical School.

Finally, the researchers bred live mice that lacked Npas4, and found evidence of neurologic problems--the mice appeared anxious and hyperactive and were prone to seizures.

Greenberg and colleagues are now trying to learn more about the wide variety of genes that Npas4 regulates, each of which could give clues to synapse development and reveal new treatment possibilities for neurologic disorders. "If you have your hand on a transcription factor such as Npas4, new genome-wide technology allows you to essentially identify every target of the transcription factor," says Greenberg. One such target is neurotrophic factor (BDNF), which Greenberg and colleagues previously showed to regulate the maturation and function of inhibitory synapses.

Children's researchers Takao Hensch, PhD, and Michela Fagiolini, PhD, also in the Neurobiology program, plan to study the Npas4-lacking mice to see if they have abnormalities in the initiation of critical periods; colleague Chinfei Chen, MD, PhD, will also study the mice, further probing how their synapses develop.

 

Copyright 2008- American Society of Registered Nurses (ASRN.ORG)-All Rights Reserved



 
1.3k
Shares
 

Articles in this issue:

Masthead

  • Masthead

    Editor-in Chief:
    Kirsten Nicole

    Editorial Staff:
    Kirsten Nicole
    Stan Kenyon
    Robyn Bowman
    Kimberly McNabb
    Lisa Gordon
    Stephanie Robinson

    Contributors:
    Kirsten Nicole
    Stan Kenyon
    Liz Di Bernardo
    Cris Lobato
    Elisa Howard
    Susan Cramer

Leave a Comment

Please keep in mind that all comments are moderated. Please do not use a spam keyword or a domain as your name, or else it will be deleted. Let's have a personal and meaningful conversation instead. Thanks for your comments!

Image Captcha