Local synaptic integration enables ON-OFF asymmetric and layer-specific visual information processing in vGluT3 amacrine cell dendrites

A basic scheme of neuronal organization in the mammalian retina is the segregation of ON and OFF pathways in the inner plexiform layer (IPL), where glutamate is released from ON and OFF bipolar cell terminals in separate inner (ON) and outer (OFF) sublayers in response to light intensity increments and decrements, respectively. However, recent studies have found that vGluT3-expressing glutamatergic amacrine cells (GACs) generate ON-OFF somatic responses and release glutamate onto both ON and OFF ganglion cell types, raising the possibility of crossover excitation in violation of the canonical ON-OFF segregation scheme. To test this possibility, we recorded light-evoked Ca2+ responses from dendrites of individual GACs infected with GCaMP6s in mouse. Under two-photon imaging, a single GAC generated rectified local dendritic responses, showing ON-dominant responses in ON sublayers and OFF-dominant responses in OFF sublayers. This unexpected ON-OFF segregation within a small-field amacrine cell arose from local synaptic processing, mediated predominantly by synaptic inhibition. Multiple forms of synaptic inhibition compartmentalized the GAC dendritic tree and endowed all dendritic varicosities with a small-center, strong-surround receptive field, which varied in receptive field size and degree of ON-OFF asymmetry with IPL depth. The results reveal a form of short-range dendritic autonomy that enables a small-field, dual-transmitter amacrine cell to process diverse dendritic functions in a stratification level-and postsynaptic target-specific manner, while preserving the fundamental ON-OFF segregation scheme for parallel visual processing and high spatial resolution for small object motion and uniformity detection.