Gbx2 Identifies Two Amacrine Cell Subtypes with Distinct Molecular, Morphological, and Physiological Properties

Abstract

Our understanding of how the nervous system works is limited by our ability to identify the neuronal subtypes that comprise functional circuits. Using a genetic approach, we show that the transcription factor Gbx2 labels two amacrine cell (AC) subtypes in the mouse retina that have distinct morphological, physiological, and molecular properties. Using a combination of RNAseq, genetic labeling, and 2p-guided whole cell patch clamp recordings, we show that one Gbx2+ AC subtype is GABAergic with a medium sized dendritic arbor that receives excitatory input from On bipolar cells. The other Gbx2+ AC population is a previously uncharacterized non-GABAergic, non-Glycinergic (nGnG) AC subtype that lacks expression of standard neurotransmitter markers. Gbx2+ nGnG ACs have smaller, asymmetric dendritic arbors that receive excitatory input from both On and Off bipolar cells. Gbx2+ nGnG ACs also exhibit spatially restricted tracer coupling to bipolar cells (BCs) through gap junctions that are modulated by dopamine signaling. This study genetically identifies a previously uncharacterized AC subtype and reveals an unusual AC-BC connectivity through gap junctions that may provide a novel model of synaptic communication and visual circuit function.