The cone presynaptic terminal is highly invaginated, with ribbons of glutamate-containing vesicles above each invagination. Cones respond to changes in light with graded changes in membrane potential. Decreases in light intensity depolarize cones and increase glutamate release, which then activates a class of cells known as Off bipolar cells.
In the new report, DeVries et al. show that Off bipolar cell dendrites contact cone terminals at two sites. Most subtypes of Off bipolar cells contact the base of the cone terminal, ∼300 nm away from the vesicle fusion sites. The group found, however, that one Off cell subtype extended its dendrites up into each invagination to end close to fusion sites.
These contacts within invaginations experienced large, rapid fluctuations in glutamate levels when a cone was depolarized. Glutamate then spilled out of the invaginations to the basal contacts. In spite of their distance from release sites, even a single vesicle's worth of glutamate was able to reach and activate these cells. Distance exacted a toll, however, as the glutamate concentrations sensed by these cells fluctuated more slowly and at much lower levels.
The invaginating cell senses glutamate via AMPA receptors, which recover rapidly from glutamate-induced desensitization and can thus decode rapid consecutive pulses. Basal cells instead use kainate receptors, which have much slower recovery times and produce responses that average over rapid fluctuations in glutamate concentration. The basally located Off bipolar cells thus generate more sustained responses.
The steady signal conveys the basic sight information of change magnitude and duration. The transient signal saying just that there was a change “is probably very important,” says DeVries, “because it can help an animal avoid predators or moving objects.”