Electrical events in neurons occur on the order of milliseconds, but the brain can process and reproduce intervals millions of times longer. We present what we believe to be the first neuronal mechanism for timing intervals longer than a few seconds. The activation and gradual relaxation of calcium-independent CaMKII measure a 6-min time window to coordinate two male-specific events during Drosophila mating: sperm transfer and a simultaneous decrease in motivation. We localize these functions to four neurons whose electrical activity is necessary only to report the conclusion of the decline in CaMKII's activity, not for the measurement of the interval. The computation of elapsed time is therefore largely invisible to standard methods of monitoring neuronal activity. Its broad conservation, ubiquitous expression, and tunable duration of activity suggest that CaMKII may time a wide variety of behavioral and cognitive processes.

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Under the right conditions any drive can overcome nearly any other, yet studies of 1 behavioural selection predominantly focus on only one, or occasionally two behaviours. 2We present an experimental and computational framework that captures and explains the 3 resolution of conflicts between several competing motivations. We characterize neurons 4 that integrate information from all rival drives to generate an aggregate signal that urges 5 male Drosophila to transition out of mating. Experimental investigation of these Drive 6 Integrating Neurons (DINs) revealed time-varying, supralinear interactions among 7 competing drives that stimulate the DINs and induce a change in behaviour. Extending 8 these findings to model the interactions between all of an animal's motivations led to the 9 surprising prediction that, under many conditions, all-to-all interactions actually buffer 10 the dominant drive against challengers. We experimentally validated this prediction, 11 showing that weak drives for a variety of tertiary goals can have a profound stabilizing 12 effect on the ongoing behaviour. These results emerge only if non-linear integration of 13 other motivations occurs for each of an animal's drives, suggesting the potential 14 universality of this mechanism. Our findings emphasize the interconnectedness of 15 motivational systems and the consequent importance of considering the full motivational 16 state of an animal to understand its behaviour. 17 18 INTRODUCTION 19 Animals often have multiple unmet needs, and attempting to satisfy one generally precludes 20 pursuing the others 1 . No one drive is strictly dominant; under the right conditions the pursuit of 21 nearly any goal may be suppressed by another 2 . At some level behaviour-specific drive states 22 must therefore affect the circuitry underlying many other behaviours 3 , and this information must 23 be integrated to arrive at a consensus. The ethologist Konrad Lorenz used the metaphor of a 24 "great parliament of instincts" to describe the behaviour of animals 2 , and the philosopher and 25 mathematician Bertrand Russell noted in his Nobel Prize acceptance speech that "If you wish to 26 know what men [sic] will do, you must know…the whole system of their desires with their 27 relative strengths" 4 . Nearly all studies on the interactions between competing motivations, in 28contrast, focus on the resolution between just two drives in conflict. Here we establish an 29 experimental and computational framework for examining the many interactions between 30 simultaneous drive states that must be considered to understand naturalistic decision-making. 32The mating duration of Drosophila melanogaster provides a clear and quantitative readout of the 33 interplay between competing drives: to switch behaviours the male must first terminate the 34 mating. If undisturbed, copulation will last ~23 minutes; if a dangerous situation arises, the male 35 may truncate the mating to flee, depending on both the severity of the threat and how far the 36 mating has progressed 5 ...