# Slit2/Robo1 signaling constrains image stabilization responses to preserve ethologically favorable directional asymmetry

## TL;DR

The study shows how the Slit2/Robo1 signaling system helps control eye movements to maintain natural visual balance during motion.

## Contribution

The novel finding is that Slit2/Robo1 signaling specifically refines retinal circuits to regulate image stabilization behavior.

## Key findings

- Robo1 and Slit2 are selectively expressed in retinal components of the accessory optic system.
- Loss of Slit2 or Robo1 increases OKR gain and reduces directional asymmetry.
- Slit2 loss in SACs enhances oDSGC firing and downstream AOS activation.

## Abstract

Visual sensation relies on retinal circuitry to receive environmental inputs and convey relevant information for behavioral outputs. Many species depend on gaze stabilization behaviors, such as the optokinetic reflex (OKR), to perceive and correct for global motion. OKR calculation begins in the retina, where ON direction-selective ganglion cells (oDSGCs) respond to slow visual motion and deliver information to the accessory optic system (AOS) to inform oculomotor outputs. Here, we find that the guidance receptor roundabout-1 (Robo1) and its ligand Slit2 are selectively expressed in mammalian retinal AOS components and refine oDSGC circuitry to constrain OKR gain for appropriate image stabilization responses. Robo1 or Slit2 loss-of-function (LOF) mutants exhibit an increase in OKR gain, reducing directional asymmetry by elevating naturally weaker OKR responses. These behavioral enhancements largely arise from alterations in the retina, and loss of Slit2 in starburst amacrine cells (SACs) enhances oDSGC firing properties, with increased spike responses, excitatory synaptic puncta, and downstream AOS activation. These findings reveal that the Slit2/Robo1 signaling tunes oDSGC circuitry to maintain regulated image stabilization behavior.

Kiraly et al. show that Slit2/Robo1 signaling refines ON direction-selective ganglion cell synapses to constrain the optokinetic reflex and conserve image tracking asymmetries commensurate with balancing optic flow biases during self-motion. These findings reveal how retinal motion detection favorably influences the magnitude of eye movements for ethological relevance.