![]() ![]() These findings reveal complex synaptic features in the rod pathway that may underlie distinct transformations of ON and OFF signals during night vision. By manipulating the membrane potential of all AIIs to span their voltage range across diverse lighting conditions, we found that AII signal transfer varies with the level of network activity: in a relatively depolarized steady-state, AIIs transmit both transient and sustained signals received from individual RBCs. ![]() We found that AIIs transmit transient and sustained signals to (ON) CBC5 but primarily transient signals to (OFF) CBC2, depending on the steady-state AII membrane potential. Finally, we recorded from RBCs and CBCs simultaneously to examine how synaptic signals are transformed by the AIIs in-between. Paired recordings between AIIs and CBC2s indicated that AIIs are also capable of transient and sustained release, consistent with capacitative exocytosis measurements in AIIs. Simultaneous whole-cell recordings confirmed that RBCs transmit transient and sustained signals to AIIs. SBEM shows that CBC2 provides, in turn, almost all of the OFF-layer ribbon synaptic input to AIIs, but electrophysiological experiments indicated weak CBC→AII signaling. Consistent with recent reports, we found that AIIs make about half of their inhibitory outputs onto one OFF CBC subtype (CBC2). We have examined these issues in mouse retina, first with serial block-face scanning electron microscopy (SBEM ) to examine synaptic connectivity between RBCs, AIIs and OFF CBCs. The input-output characteristics of AIIs also may depend on the level of network activation, which influences analog signaling in the rod pathway. Additionally, AIIs may transmit distinct signals to ON and OFF CBCs through electrical and chemical synapses, respectively. AIIs might relay transient (contrast) signals directly to OFF GCs (e.g., ) and sustained (luminance) signals to CBC terminals, leaving CBC ribbon synapses to compute contrast in the same way as RBCs. It is unknown whether AIIs transmit both components to their postsynaptic targets. Synaptic transmission from RBCs to AIIs comprises transient and sustained components that, during light responses, convey information about visual contrast and luminance, respectively. Also see Figure S1 for sequential EM images above and below those shown in C-E. iii: outline of key features in ii, showing ribbons, membranes and vesicles. i: arrowheads indicate presynaptic ribbons or vesicle clusters. D and E show reciprocal synapses between the same CBC (CBC2)-AII pair. ( C-E) SBEM examples of RBC→AII ribbon synapse, OFF CBC→AII ribbon synapse, and AII→OFF CBC conventional inhibitory synapse. ![]() Black hulls indicate ribbon synapses from two RBCs. iii, convex hulls encompassing each AII’s output synapses (darker, “central” AIIs were used to quantify connectivity). ( B) Reconstructed skeletons of 12 AII amacrine cells ( i, ii). AIIs) within a microcircuit to filter and propagate information to downstream neurons. These findings highlight specific synaptic and circuit-level features that allow intermediate neurons (e.g. Serial block-face electron microscopy (SBEM) reconstructions indicate that AIIs preferentially connect to one OFF CBC subtype (CBC2) paired whole-cell patch clamp recordings demonstrate that, depending on the level of network activation, AIIs transmit distinct components of synaptic input from single RBCs to downstream ON and OFF CBCs. Here, we dissect a microcircuit in the mouse retina in which scotopic visual information (i.e., single photon events, luminance, contrast) is encoded by rod bipolar cells (RBCs) and distributed to parallel ON and OFF cone bipolar cell (CBC) circuits via the AII amacrine cell, an inhibitory interneuron. To understand computation in a neural circuit requires a complete synaptic connectivity map and a thorough grasp of the information processing tasks performed by the circuit. ![]()
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