ON and OFF bipolar cells both express D1 receptors but not D2 (Fan and Yazulla, 2005 and Yu and Li, 2005). AT13387 research buy D1 receptors act through Gs proteins which couple to adenylyl cyclase to increase cAMP and direct activation of adenylyl cyclase by forskolin also increases bipolar Ca2+ responses ( Heidelberger and Matthews, 1994). A possible explanation for the contrasting effect in ON versus OFF could be differential sensitivity of the Cav channels to cAMP that may reflect which Cav channels underlie the response
( Pan et al., 2001 and Logiudice et al., 2006). An alternative possibility is that the ON and OFF channels are regulated by a second neuromodulator, which interacts with dopamine pathways. For instance, Iuvone and Gan (1995) have demonstrated that activation of MT2 melatonin receptors antagonizes signaling through D1 dopamine receptors in bipolar cells by inhibiting cAMP synthesis through
a Gi protein, and Wiechmann and Sherry (2012) have found that MT2 melatonin receptors are localized to OFF but not ON bipolar cells in Xenopus laevis. The fast decrease in melatonin concentration that occurs after dawn might therefore act to enhance selectively the sensitivity of OFF bipolar cells to variations in dopamine levels. We did see a small population of ON bipolar cell terminals (∼9%) strongly potentiated by olfactory stimulation (Figures 1I, S1A, and S1B). Might this reflect differences in the mechanism by which glutamate released from photoreceptors act on different types
of ON bipolar cells? In zebrafish, some ON bipolar cells respond through Alectinib metabotropic glutamate receptors and others through a glutamate transporter with a large chloride conductance (Connaughton and Nelson, 2000 and Nelson and Connaughton, 2004). Although the former mechanism predominates in mixed rod-cone bipolar cells with large terminals, the latter occurs in cone bipolar cells with smaller terminals. We tested, therefore, if there was any relationship between the size of ON terminals and their response to methionine, but did not find any; i.e., the size distribution of ON terminals responding to methionine was very similar to those that did not, both varying between ∼0.6 μm and ∼5 μm in radius. We also investigated whether there might be any relation between enough the location of ON terminals within the IPL and their response to methionine and again there was not. As a consequence, at present we do not have elements to consider this as a separate subpopulation of ON bipolar cells. Our results are consistent with the hypothesis that odor stimulation reduces the conductance and shifts the V1/2 of Cav channels in bipolar terminals, with dopamine being the key mediator. This mechanism is able to explain several of the observed effects of olfactory stimulation on the transmission of visual information through bipolar cells.