This subset of ON terminals was not distinguishable from TGF-beta inhibitor others in terms of size or position in the IPL and is therefore unlikely to reflect a difference between cone-driven and mixed rod-cone bipolar cells. No significant changes in ON or OFF responses were observed over the same time window

in the absence of methionine. Although behavioral experiments showed olfactory stimulation to be ineffective in the afternoon (Maaswinkel and Li, 2003), we found that methionine administration produced a qualitatively similar but significantly smaller modulation of responses through the OFF pathway tested between 12:00 and 3:30 p.m. (Figures S1C–S1F). Many retinal neurons signal fluctuations in light intensity

at frequencies up to ∼20 Hz. To test the effects of an olfactory stimulus on the signaling of temporal contrast, we modulated full-field stimuli at 5 Hz and measured the SyGCaMP2 signal (5 fish, n = 122 terminals). Figure 2 shows that the most obvious effect of an increase in contrast was a steady offset in the SyGCaMP2 signal, reflecting a net accumulation of calcium. A change in the SyGCaMP2 signal in the absence of a change in the mean luminance demonstrates CP-868596 ic50 a strong rectification in the bipolar cell terminal. The relation between the amplitude of the steady SyGCaMP2 signal (A) and contrast (C) is shown in Figure 2B: it could be described by a simple power function of the form A = k × Cα, with α = 1.8 ± 0.1 under control conditions. Stimulation with methionine reduced the amplitude of the rectifying response at all contrasts above 20% ( Figure 2A). Furthermore, methionine increased the exponent α of the power function to 2.9 ± 0.2 (p < 0.0001). This renders OFF terminals more sensitive to higher contrasts at the expense of lower contrasts, e.g., a change in temporal contrast from 80%

to 90% caused a change of 23.5% ΔF/F0 in control versus 40% ΔF/F0 in methionine. Olfactory stimulation did not, however, affect the responses of ON bipolar cells ( Figures and 2C and 2D). We also observed a small subset of ON bipolar cells in which the DC presynaptic calcium levels were reduced by stimulation at 5 Hz, and these were also unaffected by application of methionine ( Figures S2A and S2B). The inhibition of presynaptic calcium signals by olfactory stimulation was also a function of stimulus frequency. We tested the responses of OFF terminals to frequencies between 0.2 and 25 Hz at 90% contrast (6 fish, n = 96 terminals) and found that methionine reduced the amplitude of the SyGCaMP2 signal elicited by stimuli below 10 Hz. Again this effect was specific to the OFF pathway (Figures S2C–S2H).