Cones in the vertebrate retina project to horizontal and bipolar cells and
the horizontal cells feedback negatively to cones. This organization forms
the basis for the center/surround organization of the bipolar cells, a fund
amental step in the visual signal processing. Although the surround respons
es of bipolar cells have been recorded on many occasions, surprisingly the
underlying surround-induced responses in cones are not easily detected. In
this paper, the nature of the surround-induced responses in cones is studie
d. Horizontal cells feed back to cones by shifting the activation function
of the calcium current in cones to more negative potentials. This shift inc
reases the calcium influx, which increases the neurotransmitter. release of
the cone. In this paper, we will show that under certain conditions, in ad
dition to this increase of neurotransmitter release, a calcium-dependent ch
loride current will be activated, which polarizes the cone membrane potenti
al. The question is, whether the modulation of the calcium current ol the p
olarization of the cone membrane potential is the major determinant for fee
dback-mediated responses in second-order neurons. Depolarizing light respon
ses of biphasic horizontal cells are generated by feedback from monophasic
horizontal cells to conies, It was found that niflumic acid blocks the feed
back-induced depolarizing responses in cones, while the shift of the calciu
m current activation function and the depolarizing biphasic horizontal cell
responses remain intact. This shows that horizontal cells can feed back to
cones, without inducing major changes in the cone membrane potential. This
makes the feedback synapse from horizontal cells to cones a unique synapse
. Polarization of the presynaptic (horizontal) cell leads to calcium influx
in the postsynaptic cell (cone), but due to the combined activity of the c
alcium current and the calcium-dependent chloride current, the membrane pot
ential of the postsynaptic cell will be hardly modulated, whereas the outpu
t of the postsynaptic cell will be strongly modulated. Since no polarizatio
n of the postsynaptic cell is needed for these feedback-mediated responses,
this mechanism of synaptic transmission call modulate the neurotransmitter
release in single synaptic terminals without affecting the membrane potent
ial of the entire cell.