PT - JOURNAL ARTICLE AU - Bo Qin AU - Tim-Henning Humberg AU - Anna Kim AU - Hyong Kim AU - Jacob Short AU - Fengqiu Diao AU - Benjamin H. White AU - Simon Sprecher AU - Quan Yuan TI - Temporal control of inhibition <em>via</em> muscarinic acetylcholine receptor signaling generates ON and OFF selectivity in a simple visual circuit AID - 10.1101/535427 DP - 2019 Jan 01 TA - bioRxiv PG - 535427 4099 - http://biorxiv.org/content/early/2019/02/01/535427.short 4100 - http://biorxiv.org/content/early/2019/02/01/535427.full AB - ON and OFF selectivity in visual processing is encoded by parallel pathways that respond to either increments or decrements of light. Despite lacking anatomical features to support split channels, Drosophila larvae effectively perform visually-guided behaviors. To understand principles guiding visual computation in this simple circuit, we focus on the physiological properties and behavioral relevance of larval visual interneurons and elucidate their functions in visual processing. We find that the ON vs. OFF discrimination in the larval visual circuit emerges through light-elicited cholinergic signaling that depolarizes the cholinergic interneuron (cha-lOLP) and hyperpolarizes the glutamatergic interneuron (glu-lOLP). Genetic studies further indicate that muscarinic acetylcholine receptor (mAchR)/Gαo signaling in glu-lOLP separates the ON and OFF signals through temporal delays, the disruption of which strongly impacts both physiological responses of downstream projection neurons and dark-induced pausing behavior. Together, our studies identify cellular and molecular substrates for OFF detection in the larval visual circuit and suggests temporal control of inhibition functions as an effective strategy in generating ON and OFF selectivity without anatomical segregation.