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."
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/.
Karen Finney | EurekAlert!
Rutgers-led innovation could spur faster, cheaper, nano-based manufacturing
14.02.2018 | Rutgers University
New study from the University of Halle: How climate change alters plant growth
12.01.2018 | Martin-Luther-Universität Halle-Wittenberg
A newly developed laser technology has enabled physicists in the Laboratory for Attosecond Physics (jointly run by LMU Munich and the Max Planck Institute of Quantum Optics) to generate attosecond bursts of high-energy photons of unprecedented intensity. This has made it possible to observe the interaction of multiple photons in a single such pulse with electrons in the inner orbital shell of an atom.
In order to observe the ultrafast electron motion in the inner shells of atoms with short light pulses, the pulses must not only be ultrashort, but very...
A group of researchers led by Andrea Cavalleri at the Max Planck Institute for Structure and Dynamics of Matter (MPSD) in Hamburg has demonstrated a new method enabling precise measurements of the interatomic forces that hold crystalline solids together. The paper Probing the Interatomic Potential of Solids by Strong-Field Nonlinear Phononics, published online in Nature, explains how a terahertz-frequency laser pulse can drive very large deformations of the crystal.
By measuring the highly unusual atomic trajectories under extreme electromagnetic transients, the MPSD group could reconstruct how rigid the atomic bonds are...
Quantum computers may one day solve algorithmic problems which even the biggest supercomputers today can’t manage. But how do you test a quantum computer to...
For the first time, a team of researchers at the Max-Planck Institute (MPI) for Polymer Research in Mainz, Germany, has succeeded in making an integrated circuit (IC) from just a monolayer of a semiconducting polymer via a bottom-up, self-assembly approach.
In the self-assembly process, the semiconducting polymer arranges itself into an ordered monolayer in a transistor. The transistors are binary switches used...
Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale
Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...
15.02.2018 | Event News
13.02.2018 | Event News
12.02.2018 | Event News
23.02.2018 | Physics and Astronomy
23.02.2018 | Health and Medicine
23.02.2018 | Physics and Astronomy