It is also critical to understand how ACh-GABA cotransmission is regulated at the synaptic level; what synaptic circuits support this cotransmission; and more importantly, how such cotransmission subserves specific visual functions. This study directly detected ACh-GABA cotransmission from SACs to DSGCs and showed that both ACh and GABA function as classic, fast neurotransmitters at specific synapses between SACs and DSGCs. It characterized both the anatomical connectivity and the functional organization of the cholinergic and GABAergic synapses

between SACs and DSGCs. The study also discovered differential regulations of ACh and GABA releases from SACs, suggesting that the two transmitters are released from two separate vesicle populations. OSI-906 ic50 The results revealed

a high level of intricacy in the synaptic circuitry and computational capability of neurotransmitter cotransmission and suggested differential, yet synergistic, roles of ACh-GABA corelease in encoding motion sensitivity and direction selectivity. To understand the synaptic connectivity between displaced SACs and On-Off DSGCs (henceforth referred to simply as SACs and DSGCs, respectively), TSA HDAC we performed paired patch-clamp recordings in the whole-mount rabbit retina aged between postnatal days 17 and 45. A DSGC was first recorded under on-cell loose-patch clamp to determine its preferred and null directions based on the cell’s spike responses to a bright bar moving on a dark background in 12 different directions. The receptive field center of the cell was mapped by flashing a stationary spot at various positions in the receptive field so that the dendritic field, which is known to match closely the receptive field center (Yang and Masland, 1992), could be revealed without the need to examine the dendritic morphology under fluorescence illumination (Figure 1A). Dual whole-cell voltage-clamp recordings were subsequently made from the same DSGC and a neighboring SAC,

whose soma was located either within ± 10° of the preferred (or null) direction of the DSGC, or perpendicular (within 90° ± 10°) to the preferred Tolmetin null axis (intermediate direction). The dendrites of the SAC were estimated to overlap about half of the DSGC’s dendritic field from the preferred, null, or intermediate side (Figure 1B). Depolarizing the SAC with a series of voltage pulses in 10 mV amplitude increments (from a holding potential of −70 mV) evoked, in the postsynaptic DSGC, inward synaptic currents at −70 mV (near the Cl− equilibrium potential, ECl) and outward synaptic currents at 0 mV (near the cation reversal potential, ECat) (Figure 1B). The inward currents consisted primarily of an early component with fast rising and decaying kinetics, whereas the outward currents contained both an initial fast component and a sustained component that outlasted the duration of the presynaptic depolarization pulse.