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The interplay between the activity of neuronal circuits, their modulation by neuropeptides, and the resulting behavior, is still poorly understood. Here, we present a quantitative framework to study the relationships between the temporal pattern of activity of peptidergic neurons and of motoneurons during\n                    <jats:italic>Drosophila<\/jats:italic>\n                    ecdysis behavior, a highly stereotyped motor sequence that is critical for insect growth. We analyzed, in the time and frequency domains, simultaneous intracellular calcium recordings of peptidergic CCAP (crustacean cardioactive peptide) neurons and motoneurons obtained from isolated central nervous systems throughout fictive ecdysis behavior induced\n                    <jats:italic>ex vivo<\/jats:italic>\n                    by Ecdysis triggering hormone. We found that the activity of both neuronal populations is tightly coupled in a cross-frequency manner, suggesting that CCAP neurons modulate the frequency of motoneuron firing. To explore this idea further, we used a probabilistic logistic model to show that calcium dynamics in CCAP neurons can predict the oscillation of motoneurons, both in a simple model and in a conductance-based model capable of simulating many features of the observed neural dynamics. Finally, we developed an algorithm to quantify the motor behavior observed in videos of pupal ecdysis, and compared their features to the patterns of neuronal calcium activity recorded\n                    <jats:italic>ex vivo<\/jats:italic>\n                    . We found that the motor activity of the intact animal is more regular than the motoneuronal activity recorded from\n                    <jats:italic>ex vivo<\/jats:italic>\n                    preparations during fictive ecdysis behavior; the analysis of the patterns of movement also allowed us to identify a new post-ecdysis phase.\n                  <\/jats:p>","DOI":"10.1371\/journal.pcbi.1008933","type":"journal-article","created":{"date-parts":[[2021,12,15]],"date-time":"2021-12-15T13:38:12Z","timestamp":1639575492000},"page":"e1008933","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Extracting temporal relationships between weakly coupled peptidergic and motoneuronal signaling: Application to Drosophila ecdysis behavior"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2914-7818","authenticated-orcid":true,"given":"Miguel","family":"Pi\u00f1eiro","sequence":"first","affiliation":[]},{"given":"Wilson","family":"Mena","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6806-3628","authenticated-orcid":true,"given":"John","family":"Ewer","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0332-8098","authenticated-orcid":true,"given":"Patricio","family":"Orio","sequence":"additional","affiliation":[]}],"member":"340","published-online":{"date-parts":[[2021,12,15]]},"reference":[{"key":"pcbi.1008933.ref001","doi-asserted-by":"crossref","first-page":"1512","DOI":"10.1126\/science.7878473","article-title":"Storage of 7 +\/- 2 short-term memories in oscillatory subcycles","volume":"267","author":"JE Lisman","year":"1995","journal-title":"Science"},{"key":"pcbi.1008933.ref002","doi-asserted-by":"crossref","first-page":"7212","DOI":"10.1073\/pnas.1015297108","article-title":"Deficit in switching between functional brain networks underlies the impact of multitasking on working memory in older adults","volume":"108","author":"WC Clapp","year":"2011","journal-title":"Proc Natl Acad Sci"},{"key":"pcbi.1008933.ref003","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1007\/BF00962716","article-title":"Synchronous oscillations in neuronal systems: mechanisms and functions","volume":"1","author":"CM Gray","year":"1994","journal-title":"J Comput Neurosci"},{"key":"pcbi.1008933.ref004","doi-asserted-by":"crossref","first-page":"1872","DOI":"10.1126\/science.265.5180.1872","article-title":"Encoding of olfactory information with oscillating neural assemblies","volume":"265","author":"G Laurent","year":"1994","journal-title":"Science"},{"key":"pcbi.1008933.ref005","doi-asserted-by":"crossref","first-page":"2993","DOI":"10.1523\/JNEUROSCI.14-05-02993.1994","article-title":"Odorant-induced oscillations in the mushroom bodies of the locust","volume":"14","author":"G Laurent","year":"1994","journal-title":"J Neurosci"},{"key":"pcbi.1008933.ref006","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1038\/384162a0","article-title":"Odour encoding by temporal sequences of firing in oscillating neural assemblies","volume":"384","author":"M Wehr","year":"1996","journal-title":"Nature"},{"key":"pcbi.1008933.ref007","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1016\/j.conb.2004.10.011","article-title":"Pacemaker neurons and neuronal networks: an integrative view","volume":"14","author":"J-M Ramirez","year":"2004","journal-title":"Curr Opin Neurobiol"},{"key":"pcbi.1008933.ref008","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1016\/j.neuron.2006.11.008","article-title":"Biological pattern generation: the cellular and computational logic of networks in motion","volume":"52","author":"S. 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