A neuronal population clock for interval timing in Drosophila

Understanding the order and duration of events is fundamental to prediction and anticipation. Here, we show that Drosophila estimate, remember, and reproduce intervals in the range of several seconds. This inner sense of time relies on a population clock in the mushroom bodies. Following an olfactory cue, the Kenyon cell (KC) ensemble generates a continuous representation of time from odor onset to odor offset and beyond, with different neurons responding maximally at characteristic, odor-specific delays. The temporally sparse and dispersed KC responses are combined by mushroom body output neurons (MBONs) that each connect to hundreds of presynaptic KCs through dopamine-adjustable synapses. Brief dopamine applications reduce the weights of concurrently active KC-to-MBON connections, creating notches of depression in MBON responses driven by KC population activity. Pairing two odors with two reinforcement delays reduces MBON firing and elicits conditioned behavior at the correct, odor-specific latencies. The mushroom bodies thus form a cerebellum-like adaptive filter for predicting temporal relationships between events.