Rods signal over a 100000-fold range of light intensities, using two pathways to communicate with postsynaptic neurons. At the dimmest intensities, small rod signals (less than -2 mV) flow to rod bipolar cells where a metabotropic glutamate receptor-linked cascade provides temporal and threshold filtering. At brighter intensities, larger rod signals (up to -25 mV) flow to cone photoreceptors over a second pathway mediated by rod-cone gap junctions. Anatomical evidence for a third pathway was first obtained in the ground squirrel and subsequently in other mammals. This pathway involves direct contacts between a rod terminal and the dendrites of a subset of Off cone bipolar cells. The function of the third pathway is unclear. However, if functional, this third pathway can be used to measure the temporal properties of rod transmitter release since Off bipolar cells contain rapidly-responding AMPA/kainate receptors rather than the more slowly responding metabotropic receptors of On bipolar cells. Measurements at an amphibian rod to Off bipolar cell synapse suggest that release kinetics are matched to the slow time course of the rod photoresponse. Our previous work identify that rods may signal directly to b2 Off bipolar cells at synapses that use AMPA-type receptors. We also found that although rod-initiated responses were smaller, when normalized, synaptic responses initiated by rods and cones had similar shapes and rise times. In addition, using pair-pulse paradigm to measure response recovery, we showed that ground squirrel rods and cones replenish their releasable pool of vesicles at similar rates. The fast kinetics of rod to b2 cone bipolar synapse indicates that this synapse may function to transmit high frequency signals under conditions where signaling in the other rod pathways is decreased by membrane and synaptic filtering. We continued our research on potential functions of this alternative rod pathway in the mammalian retina. We specifically focused on the comparative kinetics of transmission in the three rod pathways. We compared the time course of signaling at the rod Off b2 synapse with that at the rod cone Off b2 cell synapse and the cone On cone bipolar cell synapse (as a stand-in for the rod On rod bipolar cell synapse). We identified that the direct rod to b2 cell pathway is the fastest of the three. We compared the light-off (i.e., step depolarization) response kinetics at the rodOff b2 cell synapse with that at the coneOn bipolar cell synapse and the rodcone electrical synapse (followed by transmission to the b2 cell). A rod step depolarization produced a b2 cell epsc that emerged from baseline with a latency of 1.10 +/- 0.47 ms, had a 20-80% rise time of 0.59 +/- 0.34 ms, and reached a peak at 3.6 +/- 1.7 ms (n=9). The second component of the b2 cell responses, which reflecting the pathway through rod-cone coupling, has a slower rise time of 5.5 +/- 1.0 ms (n = 7) with a longer time to peak of 15.3 +/- 7.3 ms (n = 8). On cone bipolar cell responses (presumably similar to rod bipolar cell responses, as both express mGluR6) to rod step depolarization had the slowest rise times (13.5 +/- 6.1 ms;n = 12 cells), and the longest times to peak (25.9 +/- 8.9 ms). Signaling in On bipolar cells is probably limited by the kinetics of the intracellular cascade;signaling in the rod to cone pathway is limited by the RC properties of the cone membrane. These results suggest that, at light-off, the rod to Off bipolar cell pathway offers the benefit of speed and is serves as a fast rod photoreceptor signaling pathway in the mammalian retina.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAEY000448-02
Application #
7968382
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2009
Total Cost
$306,246
Indirect Cost
Name
U.S. National Eye Institute
Department
Type
DUNS #
City
State
Country
Zip Code
Li, Wei; Chen, Shan; DeVries, Steven H (2010) A fast rod photoreceptor signaling pathway in the mammalian retina. Nat Neurosci 13:414-6