A Highly Ca2+-Sensitive Pool of Vesicles Contributes to Linearity at the Rod Photoreceptor Ribbon Synapse

Abstract

Studies of the properties of synaptic transmission have been carried out at only a few synapses. We analyzed exocytosis from rod photoreceptors with a combination of physiological and ultrastructural techniques. As at other ribbon synapses, we found that rods exhibited rapid kinetics of release, and the number of vesicles in the releasable pool is comparable to the number of vesicles tethered at ribbon-style active zones. However, unlike other previously studied neurons, we identified a highly Ca(2+)-sensitive pool of releasable vesicles with a relatively shallow relationship between the rate of exocytosis and [Ca(2+)](i) that is nearly linear over a presumed physiological range of intraterminal [Ca(2+)]. The low-order [Ca(2+)] dependence of release promotes a linear relationship between Ca(2+) entry and exocytosis that permits rods to relay information about small changes in illumination with high fidelity at the first synapse in vision.

Synaptic transmission at retinal ribbon synapses

“…3, Sterling and Matthews, 2005). Vesicles appear to be arranged in a hexagonal array along the face of the ribbon (Pierantoni and McCann, 1981;Thoreson et al, 2004). The orderly array of ribbon-associated vesicles contrasts with the clustering of synaptic vesicles observed at conventional synapses.…”

“…Synaptotagmin III, a plasma membrane synaptotagmin (Sudhof, 2002(Sudhof, , 2004, was also present in the outer plexiform layers in both goldfish and mouse, although the immunolabeling was somewhat sparser in mouse . Although the role of synaptotagmin 3 in exocytosis is not yet fully understood, it is interesting to note that the in vitro, calciumdependent phospholipid-binding properties of the C2A domain of synaptotagmin 3 mirror the calcium sensitivity of the highly calcium-sensitive pool of synaptic vesicles in salamander rods better than the C2A domain of synaptotagmin I does (Sugita et al, 2002;Thoreson et al, 2004; see also Section 4).…”

“…The concentration of glutamate in the vesicle is estimated to be on the order of 100 mM (Burger et al, 1989). Vesicle diameter has been measured by EM to be 29-36 nm in goldfish bipolar cell terminals Lagnado et al, 1996) but 45-50 nm in diameter in salamander photoreceptor terminals (Lasansky, 1973;Thoreson et al, 2004). Synaptic vesicle membrane is derived from the surface membrane by endocytosis (Royle and Lagnado, 2003) but is modified by the addition of many proteins implicated in vesicle docking, priming and fusion, as described above.…”

“…Assuming a similar cytoplasmic concentration of vesicles, a mammalian rod with a terminal 2-3 μm in diameter would have 8000-27,000 vesicles within the terminal cytoplasm. Of this total pool, a much smaller number, estimated at ~700 vesicles in mammalian and amphibian rods (Rao-Mirotznik et al, 1995;Thoreson et al, 2004) as well as turtle cones (Pierantoni and McCann, 1981), is thethered to each synaptic ribbon. Bipolar cell ribbons tether a smaller number of vesicles, arranged as five rows of 11 vesicles on each ribbon face .…”

“…Under physiological conditions, the maximal rate of neurotransmitter release from rod photoreceptors is much slower than that of ON bipolar cells. Furthermore, the calcium sensitivity of exocytosis appears to be very different in these two neurons (Heidelberger et al, 1994;Rieke and Schwartz, 1996;Thoreson et al, 2004).…”