Neuroscientists identify synaptic defect in brain area involved in Fragile X syndrome

Jun 07, 2010

Researchers at India's National Centre for Biological Sciences (NCBS) and New York University's Center for Neural Science have identified novel synaptic defects in an area of the brain that is involved in the debilitating emotional symptoms of Fragile X Syndrome (FXS). FXS is the leading known genetic cause of autism and mental retardation.

The study, which appears in the journal the , is also of potential therapeutic significance—it showed that a brief pharmacological treatment is capable of correcting some of these synaptic deficits in mice genetically engineered to model FXS.

Individuals with FXS, which is caused by a mutation in a gene on the , suffer from a range of problems, such as learning disabilities, attention deficit and hyperactivity, seizures, and emotional problems related to anxiety and mood instability. To investigate the cellular and molecular basis for the emotional problems associated with FXS, neuroscientists from NCBS and NYU studied how neurons and synapses in the amygdala—a small, almond-shaped part of the brain known to mediate emotion's influence on memory—are affected in FXS model mice.

Using electrophysiological recordings from neurons in the amygdala, Sumantra Chattarji, a professor at NCBS, and Aparna Suvrathan, an NCBS graduate student, determined that there were defects on both sides of synapses in the amygdala—that is, its neurons were not properly communicating with each other. NYU Professor Eric Klann and Charles Hoeffer, a former postdoctoral fellow in the Center for Neural Science and now at NYU School of Medicine, identified the molecular correlates of these defects, giving the researchers a firm understanding of where the breakdown occurs. Together, these deficits impair the ability of neurons in the amygdala to communicate and encode information.

Their next step was to consider how to normalize communication between neurons. To do so, they focused on group I metabotropic glutmate receptors (mGluRs), which have been shown to be involved in synaptic dysfunction in other brain areas in FXS. mGluRs are receptors for glutamate, the major neurotransmitter in the brain. Specifically, the researchers found that some of the synaptic deficits could be reversed when the amygdala neurons in adult FXS model mice were treated with a drug that blocks these receptors. By blocking the functionality of these receptors, normal communication between neurons could occur.

The findings hold promise for addressing FXS.

FXS is a developmental disorder that arises early in childhood, so the results suggest that synaptic defects can be corrected pharmacologically even after the disease has had time to alter the brains of the FXS mice. The findings follow recent reports that pharmaceutical companies have conducted clinical trials in FXS individuals using compounds that block mGluRs.

Explore further: Know the brain, and its axons, by the clothes they wear

Related Stories

Recommended for you

Know the brain, and its axons, by the clothes they wear

Apr 18, 2014

(Medical Xpress)—It is widely know that the grey matter of the brain is grey because it is dense with cell bodies and capillaries. The white matter is almost entirely composed of lipid-based myelin, but ...

Turning off depression in the brain

Apr 17, 2014

Scientists have traced vulnerability to depression-like behaviors in mice to out-of-balance electrical activity inside neurons of the brain's reward circuit and experimentally reversed it – but there's ...

Rapid whole-brain imaging with single cell resolution

Apr 17, 2014

A major challenge of systems biology is understanding how phenomena at the cellular scale correlate with activity at the organism level. A concerted effort has been made especially in the brain, as scientists are aiming to ...

User comments : 0

More news stories

UAE reports 12 new cases of MERS

Health authorities in the United Arab Emirates have announced 12 new cases of infection by the MERS coronavirus, but insisted the patients would be cured within two weeks.

Filipino tests negative for Middle East virus

A Filipino nurse who tested positive for the Middle East virus has been found free of infection in a subsequent examination after he returned home, Philippine health officials said Saturday.

NASA's space station Robonaut finally getting legs

Robonaut, the first out-of-this-world humanoid, is finally getting its space legs. For three years, Robonaut has had to manage from the waist up. This new pair of legs means the experimental robot—now stuck ...