Multimodal classification and sub-cellular compartmentalization of displaced amacrine cells in the mouse retina

PROJECT SUMMARY Among the 5 classes of neurons in the mouse retina (photoreceptors, horizontal cells, bipolar cells, amacrine cells, and retinal ganglion cells), our field has achieved complete or nearly complete classifications of all but the amacrine cells. One goal of this project is to fill part of this gap in knowledge by establishing a multimodal classification of displaced amacrine cells (dACs). However, unlike many other types of neurons, amacrine cells (ACs) either have no axons or they have multiple axons that may transmit different information to different locations. Thus, a second goal of this project is to go beyond somatic recordings to measure the subcellular compartmentalization critical to revealing the role amacrine cells play in retinal circuits. We have measured light responses, intrinsic electrical properties, and morphology from over 100 dACs and clustered them into 21 types. In Aim 1, we will align these morpho-electric types to transcriptomic clusters from the published single-cell RNA-seq databases. In Aims 2 and 3, we will use two-photon calcium imaging to measure functional compartmentalization within dAC neurites. The successful completion and publication of this project will have major impacts on retinal neuroscience. As we did for RGCs at rgctypes.org, we will create a website to disseminate our multimodal dAC classification data, providing a common foundation for future work across labs. Our biophysical and functional measurements of compartmentalization in dACs will combine with existing and emerging connectomic data, leading to a more complete understanding of their roles in many circuits. In Aim 3, we will use orientation selectivity as a model for a computation that may take place at the level of neurites rather than at the level of an integrated signal in the soma. Ultimately, revealing the roles of amacrine cells in retinal computation will help us understand their dysfunction in disease. The high degree of conservation of these cells from mice to humans suggests that some of the circuits we discover may translate to new interventions for blinding diseases in patients.