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The Vollum Institute is a privately endowed research institute at Oregon Health & Science University dedicated to basic research that will lead to new treatments for neurological and psychiatric diseases. Vollum scientists have broad-ranging interests that coalesce around molecular neurobiology and cellular physiology. Their work has transformed the field of neuroscience and, in particular, have provided important advances in the study of synaptic transmission, neuronal development, neurotransmitter transporters, ion channels and the neurobiology of disease.
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More about Dr. Freeman's research
Glia are cells in the brain that were long thought to be "helpers" that support neurons to perform their functions. Dr. Freeman has shown that the most predominant and least-studied glial cell, the star-shaped astrocyte, is essential to the brain's signaling network and allows for many complex behavioral outputs. His research has shown that neuromodulators, a messenger that regulates a diverse group of neurons, function not only through neurons, but signal through astrocytes as well. Currently, his research explores how neurons and glia cells communicate with one another so the nervous system runs smoothly and how their dysfunction can result in neurological disease.
Axons, slender nerve fibers, must remain intact to function, and, in cases of injury or disease, they break. His research team exploited the unique set of genetic tools available in fruit flies to label specific subsets of neurons in the intact animal, cut axons to induce degeneration, and then systematically broke each gene in the fly genome to determine which were required to promote axon destruction. They discovered that when dSarm/Sarm1 was deleted it completely blocked axon degeneration, and went on to show the same was true in mice and human cell lines. Remarkably, Freeman and colleagues have recently found that blocking the Sarm1 pathway alleviates nearly all pathological effects of traumatic brain injury in mice, and other labs have implicated Sarm1 signaling in peripheral neuropathy. These findings indicate that if researchers can find a way to block the genes that drive degeneration after injury—something Freeman's lab is currently pursuing—there's an opportunity to save the nervous system from degeneration in many cases of injury or neurodegenerative disease.
A team of scientists, led by Marc Freeman, recently demonstrated that neurons release neurotransmitters that bind astrocytes and change astrocyte calcium signaling, which in turn regulates downstream neurons. The research was published online Nov. 9 in the journal Nature. Co-authors include Zhiguo Ma and Tobias Stork of the Howard Hughes Medical Institute and Dwight E. Bergles of Johns Hopkins University.
Learn more in OHSU Research News
Read the abstract in PubMed
Researchers in Eric Gouaux's lab (Steven E. Mansoor, Wei Lü, and Wout Oosterheert) along with collaborators (Emad Tajkhorshid and Mrinal Shekhar) have solved the structures of each of the iconic conformational states of the human P2X3 receptor, giving novel insight into the mechanisms of receptor activation, desensitization and antagonism. This receptor is a non-selective cation channel that belongs to a family of purinergic receptors which are known to play important roles in cardiovascular, neuronal and immune systems. The article was published online, September 14, 2016, in the journal Nature.
Read the OHSU news release
Neuromodulators signal through astrocytes to alter neural circuit activity and behaviour
Zhiguo Ma, Tobias Stork, Dwight E. Bergles, Marc R. Freeman
Nature, 2016 Nov 9; 539(7629):428-432
Postsynaptic, not presynaptic NMDA receptors are required for spike-timing-dependent LTD induction
Brett C. Carter, Craig E. Jahr
Nature Neuroscience, 2016 Sep; 19(9):1218-1224
X-ray structures define human P2X3 receptor gating cycle and antagonist action
Steven E. Mansoor, Wei Lü, Wout Oosterheert, Mrinal Shekhar, Emad Tajkhorshid, Eric Gouaux
Nature, 2016 Sep 14; 538(7623):66-71