Interspike intervals within retinal spike bursts combinatorially encode multiple stimulus features

Neurons in various regions of the brain generate spike bursts. While the number of spikes within a burst has been shown to carry information, information coding by interspike intervals (ISIs) is less well understood. In particular, a burst with k spikes has k−1 intraburst ISIs, and these k−1 ISIs could theoretically encode k−1 independent values. In this study, we demonstrate that such combinatorial coding occurs for retinal bursts. By recording ganglion cell spikes from isolated salamander retinae, we found that intraburst ISIs encode oscillatory light sequences that are much faster than the light intensity modulation encoded by the number of spikes. When a burst has three spikes, the two intraburst ISIs combinatorially encode the amplitude and phase of the oscillatory sequence. Analysis of trial-to-trial variability suggested that intraburst ISIs are regulated by two independent mechanisms responding to orthogonal oscillatory components, one of which is common to bursts with a different number of spikes. Therefore, the retina encodes multiple stimulus features by exploiting all degrees of freedom of burst spike patterns, i.e., the spike number and multiple intraburst ISIs.Author summary: Neurons in various regions of the brain generate spike bursts. Bursts are typically composed of a few spikes generated within dozens of milliseconds, and individual bursts are separated by much longer periods of silence (~hundreds of milliseconds). Recent evidence indicates that the number of spikes in a burst, the interspike intervals (ISIs), and the overall duration of a burst, as well as the timing of burst onset, encode information. However, it remains unknown whether multiple ISIs within a single burst encode multiple input features. Here we demonstrate that such combinatorial ISI coding occurs for spike bursts in the retina. We recorded ganglion cell spikes from isolated salamander retinae stimulated with computer-generated movies. Visual response analyses indicated that multiple ISIs within a single burst combinatorially encode the phase and amplitude of oscillatory light sequences, which are different from the stimulus feature encoded by the spike number. The result demonstrates that the retina encodes multiple stimulus features by exploiting all degrees of freedom of burst spike patterns, i.e., the spike number and multiple intraburst ISIs. Because synaptic transmission in the visual system is highly sensitive to ISIs, the combinatorial ISI coding must have a major impact on visual information processing.