Synapse-specific direction selectivity in retinal bipolar cell axon terminals

Abstract

The ability to encode the direction of image motion is fundamental to our sense of vision. Direction selectivity along the four cardinal directions is thought to originate in direction-selective ganglion cells (DSGCs), due to directionally-tuned GABAergic suppression by starburst cells. Here, by utilizing two-photon glutamate imaging to measure synaptic release, we reveal that direction selectivity along all four directions arises earlier than expected, at bipolar cell outputs. Thus, DSGCs receive directionally-aligned glutamatergic inputs from bipolar cell boutons. We further show that this bouton-specific tuning relies on cholinergic excitation and GABAergic inhibition from starburst cells. In this way, starburst cells are able to refine directional tuning in the excitatory visual pathway by modulating the activity of DSGC dendrites and their axonal inputs using two different neurotransmitters.

Center-surround interactions underlie bipolar cell motion sensing in the mouse retina

“…3), just as those studies observed. There is one recent study, however, that does not fit into this pattern: using glutamate imaging, they provided evidence for a specialized circuit that bestows "true" DS on a subset of axon terminals in type 2 and 7 BCs (46). Critically, that study found a contribution from wide-field ACs; thus, the mechanism is likely only engaged for large moving stimuli.…”

“…On the other hand, direction selective RGCs are known to play important roles in brain functions and behaviors involving global motion information (64,94,95). Previous studies have also suggested that BCs participate in direction detection via other mechanisms (for example see (19,31,32,35,46,57) but also (33,34,42)) which raises the question of how these mechanisms work together. Given the diverse stimuli often used to probe motion processing, it is possible that distinct mechanisms of direction detection are engaged under different environmental conditions (as previously suggested in (96,97)), which could 571 ensure robust DS.…”

“…Whether or not BCs transmit this information is highly sensitive to the location of the stimulus relative to the BC's RF, as well as the cell's RF properties. Most studies that have previously examined the responses of BCs to moving stimuli did not observe any direction selective tuning in BC membrane potential (72), intracellular Ca 2+ (44), or glutamate responses (42,43) (but see (46)). All of these studies used global motion stimuli, like gratings or wide moving bars, that originated in the RF surround or outside of the RF of the recorded BCs.…”

“…More specifically, it was suggested that distinct BC types with different glutamate release kinetics (16,37,38) provide spatially offset inputs on postsynaptic SAC dendrites ("space-time" wiring, (31)), enhancing the preferred direction response. While voltageclamp recordings in the rabbit retina implicate some directional tuning in BCs (39)(40)(41), BC Ca 2+ signals and glutamate release have been observed to respond symmetrically to motion stimuli (42)(43)(44)(45) (but see (46)). Therefore, BCs have not been considered direction-tuned cells themselves and their exact role in the DS circuit remains debated.…”

Diurnal changes in the efficiency of information transmission at a sensory synapse

“…These neurons are the bridge between the photoreceptors and ganglion cells that deliver the results of retinal processing to downstream circuits 6 . The synaptic compartments of bipolar cells contribute to a number of processing tasks, from adaptive gain control to temporal filtering and the coding of motion, colour, orientation and direction 6,[16][17][18][19][20] . Bipolar cells, like sensory hair cells and electroreceptors, contain ribbon structures that supply vesicles to the active zone 21 .…”