UC Davis researchers identify brain protein for synapse development

January 29, 2010

(SACRAMENTO, Calif.) -- A new study from UC Davis Health System identifies for the first time a brain protein called SynDIG1 that plays a critical role in creating and sustaining synapses, the complex chemical signaling system responsible for communication between neurons. The research, published in the Jan.14 issue of the journal Neuron, fills a major gap in understanding the molecular foundations of higher cognitive abilities as well as some brain disorders.

"We know that synapses are essential for learning, memory and perception and suspect that imbalances in synapse formation impact disorders of the brain such as autism and schizophrenia," said Elva Diaz, assistant professor of pharmacology and senior author of the study. "Our study is the first to identify SynDIG1 as a critical regulator of these important brain connections."

The majority of synapses in the brain use glutamate as a neurotransmitter. While past research revealed that regulation of a certain class of glutamate receptor -- AMPA receptors -- are critical to communication between neurons, Diaz set out to discover novel molecular mechanisms of AMPA receptors that could support the formation and vitality of synapses.

She began by evaluating a gene (tmem90b) predicted to encode a novel transmembrane protein that is expressed exclusively in the central nervous system and highly similar across vertebrates, but otherwise not well-described. Microarray analyses revealed that this gene was expressed during synapse formation.

"I've always been interested in the discovery of new molecules, especially those with unique paths and intracellular influences," said Diaz, whose work focuses on the molecular mechanisms of brain development. "This is where answers to many disease processes can be found."

Diaz named the protein SynDIG1 -- or the synapse differentiation induced gene product -- and set out to define its role in synapse development. She and a team of molecular neurobiologists and electrophysiologists isolated cells from rat hippocampal neurons for a number of tests to understand the protein's functions.

One of the most important of those tests showed that SynDIG1 co-exists with AMPA receptors at the site of synapse formation, suggesting that it is essential to synapses in their earliest stages. Additional experiments revealed that manipulating SynDIG1 expression levels in the neurons changed both the number and quality of synapses, proving it had key roles in synapse formation as well in their lifespan and viability.

"Reducing SynDIG1 expression led to much fewer and smaller synapses, while increasing expression created more mature, stable synapses," said Diaz. "We think it is a key driver of the entire synaptic process, but we need to test this in an in vivo model before we can confidently say this is true."

Next, Diaz and her research team will test the role of SynDIG1 in live mice where the gene that encodes the protein is knocked out to determine the molecular and behavioral outcomes. She will also test the role of SynDIG1 in both early and established brain cells.

"We predict that SynDIG1 will be equally important in both new and older neurons, meaning that it has importance in both neurodevelopmental and later-onset diseases," said Diaz. "We could be on the path to redefining many brain diseases as synapse diseases instead."
-end-
The study lead author was Evgenia Kalashnikova of UC Davis. Additional Diaz lab investigators and collaborators on the research included Inderpreet Kaur, Gustavo Barisone, Bonnie Li, Tatsuto Ishimaru and James Trimmer of UC Davis; and Durga Mohapatra and Ramon Lorca of the University of Iowa.

The research was funded by grants to individual researchers from the Alfred P. Sloan Research Foundation, Whitehall Foundation, National Science Foundation, National Institute of Neurological Disorders and Stroke, and University of Iowa Office of the Vice President of Research.

The UC Davis School of Medicine is among the nation's leading medical schools, recognized for its specialty- and primary-care programs. The school offers fully accredited master's degree programs in public health and in informatics, and its combined M.D.-Ph.D. program is training the next generation of physician-scientists to conduct high-impact research and translate discoveries into better clinical care. Along with being a recognized leader in medical research, the school is committed to serving underserved communities and advancing rural health. For further information, visit the UC Davis School of Medicine Web site at http://www.ucdmc.ucdavis.edu/medschool/.

University of California - Davis Health System

Related Neurons Articles from Brightsurf:

Paying attention to the neurons behind our alertness
The neurons of layer 6 - the deepest layer of the cortex - were examined by researchers from the Okinawa Institute of Science and Technology Graduate University to uncover how they react to sensory stimulation in different behavioral states.

Trying to listen to the signal from neurons
Toyohashi University of Technology has developed a coaxial cable-inspired needle-electrode.

A mechanical way to stimulate neurons
Magnetic nanodiscs can be activated by an external magnetic field, providing a research tool for studying neural responses.

Extraordinary regeneration of neurons in zebrafish
Biologists from the University of Bayreuth have discovered a uniquely rapid form of regeneration in injured neurons and their function in the central nervous system of zebrafish.

Dopamine neurons mull over your options
Researchers at the University of Tsukuba have found that dopamine neurons in the brain can represent the decision-making process when making economic choices.

Neurons thrive even when malnourished
When animal, insect or human embryos grow in a malnourished environment, their developing nervous systems get first pick of any available nutrients so that new neurons can be made.

The first 3D map of the heart's neurons
An interdisciplinary research team establishes a new technological pipeline to build a 3D map of the neurons in the heart, revealing foundational insight into their role in heart attacks and other cardiac conditions.

Mapping the neurons of the rat heart in 3D
A team of researchers has developed a virtual 3D heart, digitally showcasing the heart's unique network of neurons for the first time.

How to put neurons into cages
Football-shaped microscale cages have been created using special laser technologies.

A molecule that directs neurons
A research team coordinated by the University of Trento studied a mass of brain cells, the habenula, linked to disorders like autism, schizophrenia and depression.

Read More: Neurons News and Neurons Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.