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

Cell Rep. 2020 Nov 17;33(7):108382. doi: 10.1016/j.celrep.2020.108382.

Abstract

Our understanding of nervous system function is limited by our ability to identify and manipulate neuronal subtypes within intact circuits. We show that the Gbx2CreERT2-IRES-EGFP mouse line labels two amacrine cell (AC) subtypes in the mouse retina that have distinct morphological, physiological, and molecular properties. Using a combination of RNA-seq, genetic labeling, and patch clamp recordings, we show that one subtype is GABAergic that receives excitatory input from On bipolar cells. The other population is a non-GABAergic, non-glycinergic (nGnG) AC subtype that lacks the 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. This study identifies a genetic tool for investigating the two distinct AC subtypes, and it provides a model for studying synaptic communication and visual circuit function.

Keywords: amacrine; electrical synapses; neural circuit; neuronal identity; retina; vision.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amacrine Cells / metabolism*
  • Amacrine Cells / physiology
  • Animals
  • Female
  • Gap Junctions / metabolism
  • Glycine / metabolism
  • Homeodomain Proteins / metabolism*
  • Homeodomain Proteins / physiology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Nerve Net / physiology
  • Neurotransmitter Agents / metabolism
  • Retina / metabolism
  • Retinal Ganglion Cells / metabolism
  • Synapses / metabolism
  • gamma-Aminobutyric Acid / metabolism

Substances

  • Gbx2 protein, mouse
  • Homeodomain Proteins
  • Neurotransmitter Agents
  • gamma-Aminobutyric Acid
  • Glycine