The Extreme Diversity Of Retinal Amacrine Cells Has Deep Evolutionary Roots

Area of Science:

• Neuroscience
• Evolutionary Biology
• Genomics

Background:

• Amacrine cells (ACs) are complex inhibitory neurons in the vertebrate retina.
• Their diversity is extensive, comparable to cortical interneurons.
• Understanding their evolutionary origins is crucial for retinal circuit comprehension.

Purpose of the Study:

• To reconstruct the evolutionary origins of amacrine cell diversity.
• To identify conserved and species-specific AC types across vertebrates.
• To establish a unified evolutionary framework for ACs.

Main Methods:

• Integration of single-cell and single-nucleus transcriptomic atlases.
• Comparative analysis across 24 vertebrate species.
• Phylogenetic analysis to identify orthologous cell types.

Main Results:

• Identification of 42 orthologous amacrine cell types (oACs) with conserved identities across vertebrates.
• Variation in AC type abundance and gene expression suggests adaptation to visual ecologies.
• AC diversity correlates with retinal ganglion cell (RGC) diversity, indicating co-evolution.

Conclusions:

• Amacrine cells likely originated from a hybrid amacrine cell-retinal ganglion cell precursor.
• Glycinergic ACs diverged early, followed by a split between RGCs and GABAergic ACs.
• A comprehensive evolutionary framework for amacrine cell diversity, development, and function is proposed.