CaMKII Measures the Passage of Time to Coordinate Behavior and Motivational State

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-...

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Bibliographic Details
Published in:	Neuron (Cambridge, Mass.) Vol. 105; no. 2; pp. 334 - 345.e9
Main Authors:	Thornquist, Stephen C., Langer, Kirill, Zhang, Stephen X., Rogulja, Dragana, Crickmore, Michael A.
Format:	Journal Article
Language:	English
Published:	United States Elsevier Inc 22-01-2020 Elsevier Limited
Subjects:	Animals Animals, Genetically Modified Automation Ca2+/calmodulin-dependent protein kinase II Calcium Calcium-Calmodulin-Dependent Protein Kinase Type 2 - metabolism Calcium-Calmodulin-Dependent Protein Kinase Type 2 - physiology Cognitive ability Drosophila Female Infertility Insects Kinases Male Motivation Motivation - physiology Neurons Neurons - physiology Sexual Behavior, Animal - physiology Sperm Threats Time Factors
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Summary:	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. •First neuronal interval timer lasting longer than a few seconds•Four male-specific neurons measure time during Drosophila mating•Slow decay of CaMKII kinase activity delays a motivational switch for 6 min•Electrical activity is required only to report the conclusion of the timer Thornquist et al. show that CaMKII’s kinase activity functions as an interval timer that slowly decays over the first 6 min of Drosophila mating, delaying sperm transfer and a simultaneous change in the motivation to continue mating.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Author contributions: K.L. performed the experiments in Fig. 1A. S.X.Z. wrote video tracking code for the experiments in Fig. 1A. S.C.T. performed all other experiments with assistance from K.L. and M.A.C. S.C.T. and M.A.C. designed the experiments and wrote the paper. All authors participated in the analysis of data.
ISSN:	0896-6273 1097-4199 1097-4199
DOI:	10.1016/j.neuron.2019.10.018