Disynaptic inhibition shapes tuning of OFF-motion detectors in Drosophila

The circuitry underlying the detection of visual motion in Drosophila melanogaster is one of the best studied networks in neuroscience. Lately, electron microscopy reconstructions, algorithmic models, and functional studies have proposed a common motif for the cellular circuitry of an elementary motion detector based on both supralinear enhancement for preferred direction and sublinear suppression for null-direction motion. In T5 cells, however, all columnar input neurons (Tm1, Tm2, Tm4, and Tm9) are excitatory. So, how is null-direction suppression realized there? Using two-photon calcium imaging in combination with thermogenetics, optogenetics, apoptotics, and pharmacology, we discovered that it is via CT1, the GABAergic large-field amacrine cell, where the different processes have previously been shown to act in an electrically isolated way. Within each column, CT1 receives excitatory input from Tm9 and Tm1 and provides the sign-inverted, now inhibitory input signal onto T5. Ablating CT1 or knocking down GABA-receptor subunit Rdl significantly broadened the directional tuning of T5 cells. It thus appears that the signal of Tm1 and Tm9 is used both as an excitatory input for preferred direction enhancement and, through a sign inversion within the Tm1/Tm9-CT1 microcircuit, as an inhibitory input for null-direction suppression. •A columnar microcircuit improves directional tuning of T5 neurons•Tm1 and Tm9 neurons provide indirect inhibitory input to T5 via CT1•CT1 inhibits T5 via GABA-receptor subunit Rdl How is null-direction suppression realized in the Drosophila OFF-motion pathway? Braun et al. demonstrate that disynaptic inhibition within a columnar microcircuit through Tm1, Tm9, and CT1 mediates null-direction suppression. They identify GABA-receptor subunit Rdl as an important player in this operation. Algorithmic modeling underlines the results.