INHIBITORY MECHANISMS DRIVE HABITUATION IN A VISUAL ESCAPE CIRCUIT

Visual stimuli rapidly trigger escape behaviors essential for survival. In Drosophila melanogaster, escape circuits are well characterized for looming threats, but much less is known about the processing and experience-dependent plasticity of static visual cues.
Here, we investigate the neuronal circuit underlying the light-off jump response and its habituation, a simple and conserved form of learning defined as a progressive reduction in response to repeated stimulation. Habituation deficits are commonly observed in animal models of autism spectrum disorder (ASD) and intellectual disability (ID), making this behavior a powerful translational readout.
We identified key excitatory circuit components required for the light-off jump response and its habituation, including the visual projection neurons LC4 and LPLC2 and the downstream giant fiber (GF) pathway. Building on the emerging model of habituation as an activity-dependent inhibitory potentiation process, we show that inhibitory signaling is critical for normal habituation: disruption of GABA receptor function in GF neurons leads to pronounced habituation deficits. Transcriptomic and connectomic analyses further reveal inhibitory local interneurons (iLNs) that form direct connections with LC4/LPLC2 and GF neurons, suggesting an inhibitory loop that attenuates circuit activity during repeated stimulation.
Our findings support a circuit model in which repeated activation of excitatory visual pathways recruits inhibitory interneurons that suppress output and drive habituation. Ongoing work uses cell-type-specific tools to test how ASD/ID-associated gene perturbations disrupt circuit plasticity.
This work reveals how circuit-level excitation–inhibition imbalance contributes to habituation deficits relevant to neurodevelopmental disorders.