Scientists have revealed the structure of key receptors in the brain that are involved in learning, memory, behavior, and mood. The new study published in the journal of Science reveals the structure of the AMPA receptor in its natural state for the first time. This discovery will bring new ideas to uncover the mechanisms behind a series of neurological disorders and diseases.

 

“There are some basic electrical switches in the brain,” said the study’s correspondent, senior scientist at the Volum Institute at the Oregon Health and Science University (OHSU) and Dr. Eric Gouaux, a researcher at the Howard Hughes Medical Institute. “If these switches don’t work properly, brain function is impaired, which can lead to a sudden onset of disease, memory loss and neurodegenerative diseases like Alzheimer’s.”

 

 

Scientists from the US Department of Energy at OHSU and the Pacific Northwest National Laboratory (PNNL) used cryo-electron microscopy and mass spectrometry to reveal the structure and subunit arrangement of AMPA receptors in rodents. The AMPA receptor is activated by the neurotransmitter glutamate to form a permeable ion channel that transmits signals throughout the cells of the nervous system. By uncovering the composition of the working structure of this receptor in rodents, scientists can separate and compare the same structures from the brains of dead humans. It is, therefore, possible to find the difference between the structure and composition of the AMPA receptor of a healthy person and the AMPA receptor of a person suffering from a neurodegenerative disease.

 

“This makes us very excited,” Gouaux said. “Although the results are not necessarily satisfactory, what we really expect is to study the differences between these receptors in the patient and the receptors of healthy people, in order to find possible treatments. If we can find new mechanisms for these diseases, they will provide new ideas for the development of new therapies.”

 

The cryo-electron microscopy technology that revolutionized structural biology laid the foundation for this research. Scientists can use freeze-transmission electron microscopy to study the structure of receptors in their natural state, which allows them to observe biomolecules at near-atom-scale levels.

 

“This is a very sensitive technology, and you only need a small number of molecules to perform the analysis,” says Gouaux. “Now we are really observing their structure in the natural state of these receptors.”

 

 

Reference

Eric Gouaux et al.Architecture and subunit arrangement of native AMPA receptors elucidated by cryo-EM” Science (2019). DOI: 10.1126/science.aaw8250