Rate of quantal excitation to a retinal ganglion cell evoked by sensory input

To determine the rate and statistics of light-evoked transmitter release from bipolar synapses, intracellular recordings were made from ON-alpha ganglion cells in the periphery of the intact, superfused, cat retina. Sodium channels were blocked with tetrodotoxin to prevent action potentials. A light bar covering the receptive field center excited the bipolar cells that contact the alpha cell and evoked a transient then a sustained depolarization. The sustained depolarization was quantified as change in mean voltage (Delta nu), and the increase in voltage noise that accompanied it was quantified as change in voltage variance (Delta sigma(2)). As light intensity increased, Delta nu and Delta sigma(2) both increased, but their ratio held constant. This behavior is consistent with Poisson arrival of transmitter quanta at the ganglion cell. The response component attributable to glutamate quanta from bipolar synapses was isolated by application of 6-cyano-7-nitroquinoxaline (CNQX). As CNQX concentration increased, the signal/noise ratio of this response component (Delta nu(CNQX)/Delta sigma(CNQX)) held constant. This is also consistent with Poisson arrival and justified the application of fluctuation analysis. Two different methods of fluctuation analysis applied to Delta nu(CNQX) and Delta sigma(CNQX) produced similar results, leading to an estimate that a just-maximal sustained response was caused by similar to 3,700 quanta s(-1). The transient response was caused by a rate that was no more than 10-fold greater. Because the ON-alpha cell at this retinal locus has similar to 2,200 bipolar synapses, one synapse released similar to 1.7 quanta s(-1) for the sustained response and no more than 17 quanta s(-1) for the transient. Consequently, within the ganglion cell's integration interval, here calculated to be similar to 16 ms, a bipolar synapse rarely releases more than one quantum. Thus for just-maximal sustained and transient depolarizations, the conductance modulated by a single bipolar cell synapse is limited to the quantal conductance (similar to 100 pS at its peak). This helps preserve linear summation of quanta. The Delta nu/Delta sigma(2) ratio remained constant even as the ganglion cell's response saturated, which suggested that even at the peak of sensory input, summation remains linear, and that saturation occurs before the bipolar synapse.