The identity of the messenger that carries the inhibitory surround receptive field signal from horizontal cells to cone photoreceptors has eluded retinal neurobiologists for nearly three decades. Encoded in horizontal cell membrane potential, the feedback signal presynaptically inhibits neurotransmitter release at the cone terminal. An interesting collection of candidate mechanisms and messengers have come, and some have gone. In this issue of the Journal of General Physiology, Hirasawa and Kaneko (2003) take a giant step forward in defining the synaptic messenger. The insight their elegant experiments offer is that protons transmit inhibitory surround information from horizontal cells to cones, and that protons subtly modulate presynaptic Ca channel activity to alter neurotransmitter release dependent on illumination of the surround. That such a ubiquitous signal, e.g., pH, is the messenger in one of the most fundamental steps in visual processing is illuminating in its own right.
Center-surround antagonism is an archetype found in every sensory system design. In visual systems, this form of lateral inhibition was first described in Limulus by Hartline (1940). Together with other pioneering work, it was established that this network of laterally interacting elements gave rise to contrast enhancement and edge detection. Ever since the first recordings in vertebrates of a cone photoreceptor response to light (Baylor et al., 1971), it has been known that illumination of the surround counter-acts illumination of the center. In the vertebrate retina, bipolar cells are the recipients of modulated photoreceptor signals and have center-surround antagonistic receptive fields, which they transmit on to the ganglion cells (Werblin and Dowling, 1969). In primate retina, we now know that surround inhibition is also mediated through presynaptic inhibition in cone photoreceptors (Verweij et al., 2003).