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Maxim Kozhemyakin, Ruth Heidelberger; CaBP5 and Munc13-2 regulate rod bipolar cell to AII amacrine cell synaptic transmission. Invest. Ophthalmol. Vis. Sci. 2019;60(9):550.
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© ARVO (1962-2015); The Authors (2016-present)
CaBP5, a member of the calmodulin (CaM)-like family of Ca2+ binding proteins, is required for normal rod-mediated light sensitivity in the mammalian retina. The rod bipolar cell (RBC) expresses CaBP5, however little is known about the role of CaBP5 in RBCs. To probe for a role in neurotransmitter release, we compared miniature-like events (ml-EPSCs) and light-evoked postsynaptic responses (le-EPSCs) in AII amacrine cells (AIIs) from CaBP5-/- mice and wild-type (WT) mice. Additionally, we examined responses from mice lacking Munc13-2-/-, a key synaptic priming protein of conventional synapses whose role at retinal ribbon synapses is unclear.
In the retinal slice preparation, AIIs were held under whole-cell voltage clamp control at -70 mV. le-EPSCs, evoked by a 100ms, 488nm light pulse, and ml-EPSCs were recorded and compared in age-matched wild-type (WT), CaBP5-/- and Munc13-2-/- mice.
The mean amplitude of AII ml-EPSCs was significantly larger in the absence of CaBP5 compared to WT and Munc13-2-/- (8.8±0.8pA, n=30156; 5.7±0.7pA, n=6162; 5.2±0.7 pA, n=8800; p<0.005). Moreover, the frequency distribution of ml-EPSCs in CaBP5-/- exhibited a second peak that was approximately double that of the first, consistent with multiquantal release. A second peak was absent from both WT and Munc13-2-/-. The inter-event interval of ml-EPSCs was significantly shorter in CaBP5-/- than in WT and Munc13-2-/-. This was attributable to a near complete loss of inter-event intervals greater than ≈70ms, whereas long inter-event intervals were evident in both WT and Munc13-2-/-. Indeed, in the absence of Munc13-2, most events occurred with an inter-event interval ≥70ms. The amplitudes of le-EPSCs were reduced by ≈50% in CaBP5-/- when compared with WT, but were approximately two times larger than in Munc13-2-/- (10.5±2.1pA, n=11; 24.1±4.3pA, n=16; 5.8±1.8pA, n=9; p<0.0001).
These results demonstrate that CaBP5 is required for normal synaptic transmission from RBCs to AII amacrine cells. CaBP5 augments light evoked release, presumably via its ability to regulate spontaneous release and the population of fusion competent vesicles, and suggests a role for CaBP5 in the modulation of synaptic gain. In addition, while not absolutely essential for exocytosis at the RBC-AII synapse, Munc13-2 is required for efficient synaptic transmission at this retinal ribbon synapse.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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