A hierarchical electrical synaptic circuit mechanism for integrative parallel visual processing in the retina

• Paired recording and 2P imaging reveal fast and slow modes of CBC transmission • Serial electrical-chemical synapses produce spatially dispersed glutamate “clouds” • BC6 functions as a driver, distributing sustained signals via a rectified hierarchy • CBC coupling boosts detection of small, low-contrast signals in retina and dLGN Paired recording and 2P imaging reveal fast and slow modes of CBC transmission Serial electrical-chemical synapses produce spatially dispersed glutamate “clouds” BC6 functions as a driver, distributing sustained signals via a rectified hierarchy CBC coupling boosts detection of small, low-contrast signals in retina and dLGN Parallel visual processing begins with retinal bipolar cells, traditionally regarded as independent chemical synaptic channels. However, the circuit-level synaptic integration of chemical and electrical synapses within this network remains unclear. Using dual patch-clamp recordings and two-photon imaging in whole-mount retina, we systematically characterized synaptic transmission across 13 mouse and 2 human cone bipolar cell (CBC) types, revealing two distinct modes: a fast, direct chemical pathway and a slower, serial electrical-chemical circuit among both ON and OFF CBCs. In mice, the slow mode generates spatially dispersed glutamate “clouds” that facilitate integration across CBC types. We discovered specific “driver” CBCs that distribute robust, sustained signals through a hierarchical, functionally rectified network, enhancing sensitivity to small, low-contrast stimuli in downstream retinal cells and thalamic neurons in awake mice. Our findings challenge the classical view of independent CBC channels, revealing an integrative, hierarchical electrical-chemical synaptic architecture that enhances visual detection and coding efficiency.