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

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.

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Mao Lab
Zhong Lab

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

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