High-Throughput Single Cell Projection Mapping and Spine Quantification in the Primate Brain by Synaptic Barcoding

The primate brain contains trillions of highly specific synaptic connections that are the building blocks of neural computation. While tools available in rodents have begun to shed light on how particular cell types and circuits participate in brain functions, these approaches are not currently possible to apply to primates. 

Recently, our labs have developed technology that: 1) delivers barcoded RNAs to the presynaptic and postsynaptic compartments with high sensitivity and specificity using AAVs; and 2) allows CNS-wide transduction by AAV through systemic injection. We will combine these innovations, together with our platforms for single-cell and spatial transcriptomics, to systematically map the projections of thousands of midbrain dopaminergic neurons across the marmoset brain. In addition, we will develop strategies for the rapid and scalable quantification of postsynaptic spines in individual cells, using known abundance in spine variation amongst the cells of the dentate gyrus as a validation. 

Together, these technologies will enable the routine quantification of presynaptic and postsynaptic phenotypes at a level of resolution and scale that has hitherto been impossible in primate.