Vollum Institute at OHSU (OHSU/Kristyna Wentz-Graff)

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, has provided important advances in the study of synaptic transmission, neuronal development, neurotransmitter transporters, ion channels and the neurobiology of disease.
Learn more about the Vollum's mission

Friday Work–In–Progress Talks

The Friday "work-in-progress" (WIP) seminars occur weekly during the academic year and provide an opportunity for postdoctoral fellows and graduate students to share their current research projects in an interactive and less formal environment.
Find out more information on how to attend and the speaker schedule.

PostDoc Career Transition Seminar Series

This week (Dec 1st), the Vollum kicks off the Postdoc Career Transition Seminar Series. This series, which lasts thru February, will highlight the scientific accomplishments and future research plans of OHSU postdocs preparing for careers as independent investigators.

Find out more information and the speaker schedule.

Research highlights

Synaptotagmin-1 is a Ca2+ sensor for somatodendritic dopamine release.
Lebowitz JJ, Banerjee A, Qiao C, Bunzow JR, Williams JT, Kaeser PS. Cell Rep. 2023 Jan 31;42(1):111915. doi: 10.1016/j.celrep.2022.111915. Epub 2022 Dec 30. PMID: 36640316; PMCID: PMC9993464.

Discoidin domain receptor regulates ensheathment, survival and caliber of peripheral axons
Corty MM, Hulegaard AL, Hill JQ, Sheehan AE, Aicher SA, Freeman MR. Development. 2022 Dec 1;149(23):dev200636. doi: 10.1242/dev.200636. Epub 2022 Dec 13. PMID: 36355066

Ascertaining cells’ synaptic connections and RNA expression simultaneously with barcoded rabies virus libraries. 
Saunders, A., Huang, K.W., Vondrak, C. et al. Nat Commun 13, 6993
(2022). doi: 10.1038/s41467-022-34334-1

Locomotion activates PKA through dopamine and adenosine in striatal neurons.
Ma L, Day-Cooney J, Benavides OJ, Muniak MA, Qin M, Ding JB, Mao T, Zhong H. Nature. 2022 Nov 9. doi: 10.1038/s41586-022-05407-4. 

Sensitive genetically encoded sensors for population and subcellular imaging of cAMP in vivo.
Massengill CI, Bayless-Edwards L, Ceballos CC, Cebul ER, Cahill J, Bharadwaj A, Wilson E, Qin M, Whorton MR, Baconguis I, Ye B, Mao T, Zhong H. Nat Methods. 2022 Nov;19(11):1461-1471. doi: 10.1038/s41592-022-01646-5. Epub 2022 Oct 27. PMID: 36303019

Fast resupply of synaptic vesicles requires synaptotagmin-3.
Weingarten DJ, Shrestha A, Juda-Nelson K, Kissiwaa SA, Spruston E, Jackman SL. Nature. 2022 Nov;611(7935):320-325. doi: 10.1038/s41586-022-05337-1. Epub 2022 Oct 19.  PMID: 36261524.

Structure of C. elegans TMC-1 complex illuminates auditory mechanosensory transduction 
Jeong, H., Clark, S., Goehring, A., Dehghani-Ghahnaviyeh, S., Tajkhorshid, E., Gouaux, E. (2022) Nature Oct;610: 796-803.

Monitoring glycolytic dynamics in single cells using a fluorescent biosensor for fructose 1,6-bisphosphate.
Koberstein JN, Stewart ML, Smith CB, Tarasov AI, Ashcroft FM, Stork PJS, Goodman RH. Proc Natl Acad Sci U S A. 2022 Aug 2;119(31):e2204407119. doi: 10.1073/pnas.2204407119. Epub 2022 Jul 26. PMID: 35881794

Resurgent Na+ currents promote ultrafast spiking in projection neurons that drive fine motor control.
Zemel BM, Nevue AA, Dagostin A, Lovell PV, Mello CV, von Gersdorff H.
   Nat Commun. 2021 Nov 19;12(1):6762. doi: 10.1038/s41467-021-26521-3.

Glycine Release Is Potentiated by cAMP via EPAC2 and Ca2+ Stores in a Retinal Interneuron
Meadows MA, Balakrishnan V, Wang X, von Gersdorff H.
J Neurosci. 2021 Nov 17;41(46):9503-9520.

Distinct in vivo dynamics of excitatory synapses onto cortical pyramidal neurons and parvalbumin-positive interneurons
Melander JB*, Nayebi A*, Jongbloets BC, Fortin DA, Maozhen Q, Ganguli S#, Mao T#, Zhong H#.
Cell Reports. 2021 Nov 9;37(6):109972. doi: 10.1016/j.celrep.2021.109972 (*contributed equally) (#co-correspondence)

Architecture and assembly mechanism of native glycine receptors
Zhu H, Gouaux E Nature 2021 Sep 23; doi: 10.1038/s41586-021-04022-z Online ahead of print

Molecular mechanism of prestin electromotive signal amplification
Ge J*, Elferich J*, Dehghani-Ghahnaviyeh S, Zhao Z, Meadows M, von Gersdorff H, Tajkhorshid E, Gouaux E
Cell 2021 Sep 2; 184(18):4669-4679.e13 (*contributed equally)

The residence of synaptically released dopamine on D2 autoreceptors
Condon AF, Robinson BG, Asad N, Dore TM, Tian L, Williams JT
Cell Reports 2021 Aug 3; 36(5):109465

View all in PubMed

Saunders Lab Awarded an R01 grant from the BRAIN Initiative to Further Develop SBARRO for In Vivo Connectivity Analysis

Saunders Lab team photo
(Back Row) Karl Young, Alex Nevue, Emily Tiedemann, Zach Goode (Front row) Lamya Ben Ameur, Hoa Trinh, Arpy Saunders Photo Credit: Chris Ghormley

Congratulations to Arpy and the Saunders Lab. Arpy has published a paper titled "Ascertaining cells’ synaptic connections and RNA expression simultaneously with barcoded rabies virus libraries" in Nature Communications. Synaptic connections are critical for brain function but are hard to measure systematically. Saunders et al report “SBARRO”, a method that uses rabies virus barcoding and single-cell RNA-seq to parallelize monosynaptic network reconstruction from molecularly-profiled single cells.

Modern theories of neuroscience suggest that selective synaptic connections among molecularly diverse brain cells are critical for brain function, but fast and systematic mapping of pre- and post-synaptic connectivity relationships remains a major unmet need. Saunders et al report a rabies virus-based method called SBARRO that enables hundreds of instances of presynaptic networks belonging to individual postsynaptic neurons to be reconstructed in parallel from single experiments using single-cell RNA sequencing. Accepted models suggest rabies virus spreads via synaptic connections. SBARRO leverages this property along with viral genomic “barcoding” to track the cell-to-cell infectivity paths of viral clones resulting from individual rabies virus infections, such that cells sharing viral barcodes belong to the same synaptic networks. Genome-wide RNA profiling assigns molecular types and states to each cell, enabling quantitative maps of cell-type-specific connectivity to be quickly built and studied in the context of host cell RNAs. Saunders et al use SBARRO libraries with millions of unique barcodes to reconstruct synaptic networks from cultured mouse brain cells. The authors discover ways in which the size and cell-type composition of presynaptic cells differ by postsynaptic cell type and identify differences in postsynaptic gene expression that associate with presynaptic network size. Leveraging the staggered development of brain cells in culture, Saunders et al further demonstrate that rabies uptake tends to occur in neurons with RNA expression patterns consistent with mature presynaptic function. These data underscore the importance of synaptic function for rabies virus transmission.

“The SBARRO approach has the potential to be transformational for researchers that have long wanted to explore problems that deal with changes in connectivity across large regions of the brain," said Marc Freeman, director of the Vollum Institute. "For instance, we have long speculated that neurodevelopmental disorders like autism spectrum disorder and schizophrenia have some basis in sweeping changes in connectivity across the brain, but have previously only been able to examine a small fraction of those connections.  SBARRO will enable us to answer this question definitively and comprehensively describe disease-associated changes in connectivity across entire brain regions with remarkable accuracy and speed.  It will be exciting to see how this powerful new approach catapults the field forward.” 

Read the full paper
Saunders Lab

Vollum Institute/OHSU scientists identify molecule that could help treat Parkinson’s

Tianyi Mao, Ph.D., and Haining Zhong, Ph.D., are scientists with the OHSU Vollum Institute
Tianyi Mao, Ph.D., and Haining Zhong, Ph.D., are scientists with the OHSU Vollum Institute. The pair's recent discovery of how adenosine operates in the brain is expected to help create new treatments for Parkinson's disease. (OHSU)

Researchers at Oregon Health & Science University have discovered that the neurotransmitter adenosine effectively acts as a brake to dopamine, another well-known neurotransmitter involved in motor control.

Scientists found that adenosine operates in a kind of push-pull dynamic with dopamine in the brain; the new discovery published today in the journal Nature.

“There are two neuronal circuits: one that helps promote action and the other that inhibits action,” said senior author Haining Zhong, Ph.D., scientist with the OHSU Vollum Institute. “Dopamine promotes the first circuit to enable movement, and adenosine is the ‘brake’ that promotes the second circuit and brings balance to the system.”

The discovery could immediately suggest new avenues of drug development to treat symptoms of Parkinson’s disease, a movement disorder where the loss of dopamine-producing cells has been widely implicated as a cause.

Scientists have long suspected that dopamine is influenced by an opposing dynamic of neuronal signaling in the striatum — a critical region of the brain that mediates movement along with reward, motivation and learning. The striatum is also the primary brain region affected in Parkinson’s disease by the loss of dopamine-producing cells.

“People for a long time suspected there has to be this push-pull system,” said co-author Tianyi Mao, Ph.D., a scientist at the Vollum who happens to be married to Zhong.

Read the Full Article
Mao Lab
Zhong Lab

Discovery gives insight into brain function, breakdowns

Dennis WEINGARTEN and Skyler Jackman
Dennis Weingarten, Ph.D., (left) post–doctoral scientist & Skyler Jackman, Ph.D., assistant scientist in the OHSU Vollum Institute, are the co-authors of a neurotransmission discovery that is published in the journal Nature. (OHSU/Christine Torres Hicks)

Scientists at Oregon Health & Science University have identified a long-sought gene-encoded protein that enables the brain to communicate a broad range of signals across gaps between neurons, known as synapses.

The discovery published today in the journal Nature.

Known as synaptotagmin-3, or SYT3, the protein helps to replenish the supply of chemical neurotransmitters that carry signals between neurons.

Read the full OHSU News article here
Jackman Lab

Gouaux Lab discovers mechanism of hearing

In a discovery published today in the journal Nature, OHSU scientists used advanced imaging to reveal the molecular machinery that allows the inner ear to convert vibrations into the sensation of sound.
In a discovery published today in the journal Nature, OHSU scientists used advanced imaging to reveal the molecular machinery that allows the inner ear to convert vibrations into the sensation of sound.

Scientists at Oregon Health & Science University have revealed, for the first time and in near-atomic detail, the structure of the key part of the inner ear responsible for hearing.

“This is the last sensory system in which that fundamental molecular machinery has remained unknown,” said senior author Eric Gouaux, Ph.D., senior scientist with the OHSU Vollum Institute and a Howard Hughes Medical Institute investigator. “The molecular machinery that carries out this absolutely amazing process has been unresolved for decades.”

Until now.

Read the Full Article Here
Gouaux Lab

More news and accolades

Recognition for our early career awardees

Graduate students and postdoctoral fellows are usually supported by research grants to individual faculty or by institutional training grants from the NIH. However, a sought-after perk for trainees is to obtain an individual fellowship from federal sources or foundations. Such awards are an honor and also provide important financial support for the trainee and their lab. Graduate students and postdoctoral fellows in the Vollum Institute have been remarkably successful in obtaining these awards over the past few years. This is a credit to the quality of the trainees and the support they receive from their mentors. Congratulations to all.

The Lacroute Fellows Program invests in School of Medicine graduate education, by supporting exceptional students performing innovative research in the Vollum/OHSU Neuroscience Graduate Program.

Congratulations to the 2022 fellows:

  • Danica Bojovic, Mishra and von Gersdorff Labs
  • Natasha Warikoo, Schnell Lab
  • Tin Long Yiu, Zhong Lab

These 1-year fellowships cover $24,000 of the student’s stipend and provide an allowance of $1,000 for related expenses, such as attending scientific conferences or courses.

Cody Call, Ph.D., Monk Lab
NINDS F32: Regulation of node of Ranvier formation and maintenance by astrocytes.

Alejandra Fernandez, Ph.D., Wright Lab
NINDS K01: “The role of Pten on primary sensory neuron development.”
Collins Medical Trust: “The role of Pten signaling in the intrinsic control of somatosensory neuron diversification.

Kevin Guttenplan, Ph.D., Freeman Lab
Helen Hay Whitney Foundation: “How do astrocytes regulate neuronal circuits?”

Dongeun Heo, Ph.D., Monk/Freeman Labs
NINDS F32: "Investigating the role of diazepam binding inhibitor (DBI) in astrocytes and neural circuit maturation."

Yunsik Kang, Ph.D., Freeman Lab
NINDS K99/ROO Pathway to Independence: “How do astrocytes remodel neuronal circuits?”

Jiaxing Li, Ph.D., Monk Lab
Warren Alpert Foundation: Investigating mechanisms of neuron-oligodendrocyte precursor cell interactions.

Cathy Spangler, Ph.D., Gouaux Lab
NIH Natl Cancer Inst: Structural and functional characterization of native AMPA receptor complexes in glioblastoma.

Landon Bayless-Edwards, Mao Lab
NIDA NRSA F30: "Intracellular signaling mechanisms underlying opioid modulation of pain"

Danica Bojovic, von Gersdorff and Mishra Labs
America Heart Association predoctoral fellowship: "Astrocyte gap junctions modulate neurovascular responses"

Hannah Collins, Monk and Emery Labs
NINDS F31: Control of CNS Myelination by the E3 Ligase Component Fbxw7

Amelia Culp, Mao Lab
National Science Foundation, Graduate Research Fellowship

Rachel de la Torre, Freeman Lab
NINDS F31: “How do glia remodel the nervous system?”

Kimberley Englen, Williams Lab
National Science Foundation, Graduate Research Fellowship

Makayla Freitas, Gouaux Lab
National Science Foundation, Graduate Research Fellowship

Jennifer Jahncke, Wright Lab
NINDS F31 Predoctoral Fellowship: "Dystroglycan regulates cerebellar synapse function"

Jennifer Jenks, Emery Lab
National Science Foundation, Graduate Research Fellowship

Omar Koita, Williams Lab
NINDS F99:Mechanistic description of tolerance/withdrawal from opioids in the paraventricular nucleus of the thalamus.

Tania Miramontes, Monk Lab
NINDS F31: "Investigating the role of cannabinoid receptors in oligodendrocyte development"

Congratulations to all of our graduate researchers in the Vollum/OHSU Neuroscience Graduate Program who received ARCS Foundation Scholar Awards from the ARCS Oregon Chapter!

First Year: Milana Krush and Jed Syrenne
Second Year: Teva Bracha and Kim Engeln
Third Year: Sweta Adhikary, Amelia Culp, Makayla Freitas and Sierra Smith

Learn more about these scholars and the ARCS Foundation Oregon

Congratulations to the Neuroscience Graduate Program researchers — Ali Pincus, Prashant Rao and Petra Richer — who received 2020 N.L. Tartar Trust Fellowships. The $2,000 grants are awarded annually by the OHSU School of Medicine as a means to support research endeavors and career development. Keep up the great work!