The Origin of the "S-Off" Signal in a Mammalian Retina

Abstract

Purpose: : Color vision is the ability to discriminate spectral variations of light regardless of variations in the intensity. In most mammals, signals from two types of cones, the short wavelength sensitive (S-) cones and the middle/long wavelength sensitive (M-) cones, are contrasted to generate S-M color opponency. Two types of S-M opponency, S-On/M-Off and S-Off/M-On, form the foundation for dichromatic color vision. The S-cone bipolar cells (SCBs) are On cells carrying "S-On" signals. However, the origin of the "S-Off" signal remains elusive. One possibility is that certain amacrine cells receive input from SCBs and, through an inhibitory synapse, reverse the S-On signal to an Off one, similar to how AII amacrine cells reverse On signals from rod bipolar cells. We set out to search for such a "blue amacrine cell" in the ground squirrel retina.

Methods: : We performed whole-cell recordings from cones, bipolar, and amacrine cells in ground squirrel retina slices. We designed an "S-cone isolating" stimulus using the silence substitution method. Two Hz sine waves of green (578 nm) and blue (435 nm) stimuli that are 180^o out of phase were presented to green cones for "live" calibration until the modulation of the membrane potential of green cones was abolished. Consequently, any inner retinal neurons that respond to this stimulus are the ones that receive prominent S-cone inputs. Fluorescent tracer was included in the recording pipette to reconstruct the recorded cells.

Results: : We identified a type of amacrine cell that responded strongly to the "S-cone isolating" stimulus. They displayed a sustained depolarizing response to a one second blue light pulse with a hyperpolarizing overshoot at light Off - appropriate for relaxing tonic inhibition and providing an Off excitatory drive to the postsynaptic cell. The reconstruction of the cells revealed long descending dendrites reaching the bottom of the IPL - suitable for receiving inputs from SCBs.

Conclusions: : The "S-Off" signal in the mammalian retina may originate from a type of amacrine cell that receives SCB input and inverts the "S-On" signal through its inhibitory output synapse.

Keywords: color vision • amacrine cells • electrophysiology: non-clinical