Cone bipolar cell synapses generate transient versus sustained signals in parallel ON pathways of the mouse retina

Parallel processing is a fundamental organizing principle in the nervous
system and understanding how parallel neural circuits generate distinct
outputs from common inputs is a key goal of neuroscience. In the mammalian
retina, divergence of cone signals into multiple feedforward bipolar cell
pathways forms the initial basis for parallel retinal circuits dedicated
to specific visual functions. Here, we used patch-clamp electrophysiology,
electron microscopy and two photon imaging of a fluorescent glutamate
sensor to examine how kinetically-distinct responses arise in transient
versus sustained ON alpha RGCs (ON-T and ON-S RGCs) of the mouse retina.
We directly compared the visual response properties of these RGCs with
their presynaptic bipolar cell partners, which we identified using 3D
electron microscopy reconstruction. Different ON bipolar cell subtypes
(type 5i, type 6 and type 7) had indistinguishable light-driven responses
whereas extracellular glutamate signals around RGC dendrites and
postsynaptic excitatory currents measured in ON-T and ON-S RGCs in
response to the identical stimuli used to probe bipolar cells were
kinetically distinct. Anatomical examination of the bipolar cell axon
terminals presynaptic to ON-T and ON-S RGCs suggests that bipolar
subtype-specific differences in the size of synaptic ribbon-associated
vesicle pools may contribute to transient versus sustained kinetics. Our
findings indicate that feedforward bipolar cell synapses are a primary
point of divergence in kinetically distinct visual pathways.