Functional circuitry of the retinal ganglion cell's nonlinear receptive field

A retinal ganglion cell commonly expresses two spatially overlapping recept ive field mechanisms. One is the familiar "center/ surround," which sums ex citation and inhibition across a region somewhat broader than the ganglion cell's dendritic field. This mechanism responds to a drifting grating by mo dulating firing at the drift frequency (linear response). Less familiar is the "nonlinear" mechanism, which sums the rectified output of many small su bunits that extend for millimeters beyond the dendritic field. This mechani sm responds to a contrast-reversing grating by modulating firing at twice t he reversal frequency (nonlinear response). We investigated this nonlinear mechanism by presenting visual stimuli to the intact guinea pig retina in v itro while recording intracellularly from large brisk and sluggish ganglion cells. A contrast-reversing grating modulated the membrane potential (in a ddition to the firing rate) at twice the reversal frequency. This response was initially hyperpolarizing for some cells (either ON or OFF center) and initially depolarizing for others. Experiments in which responses to bars w ere summed in-phase or out-of-phase suggested that the single class of bipo lar cells (either ON or OFF) that drives the center/surround response also drives the nonlinear response. Consistent with this, nonlinear responses pe rsisted in OFF ganglion cells when ON bipolar cell responses were blocked b y L-AP-4. Nonlinear responses evoked from millimeters beyond the ganglion c ell were eliminated by tetrodotoxin. Thus, to relay the response from dista nt regions of the receptive field requires a spiking interneuron. Nonlinear responses from different regions of the receptive field added linearly.