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Previously, we developed a multifunctional, multistable symmetric HCO model which produced slow locomotor-like and fast paw-shake-like activity patterns. Here, we describe asymmetric features of paw-shake responses in a symmetric HCO model and test these predictions experimentally. We considered bursting properties of the two model half-centers during transient paw-shake-like responses to short perturbations during locomotor-like activity. We found that when a current pulse was applied during the spiking phase of one half-center, let\u2019s call it #1, the consecutive burst durations (BDs) of that half-center increased throughout the paw-shake response, while BDs of the other half-center, let\u2019s call it #2, only changed slightly. In contrast, the consecutive interburst intervals (IBIs) of half-center #1 changed little, while IBIs of half-center #2 increased. We demonstrated that this asymmetry between the half-centers depends on the phase of the locomotor-like rhythm at which the perturbation was applied. We suggest that the fast transient response reflects functional asymmetries of slow processes that underly the locomotor-like pattern; e.g., asymmetric levels of inactivation across the two half-centers for a slowly inactivating inward current. We compared model results with those of in-vivo paw-shake responses evoked in locomoting cats and found similar asymmetries. Electromyographic (EMG) BDs of anterior hindlimb muscles with flexor-related activity increased in consecutive paw-shake cycles, while BD of posterior muscles with extensor-related activity did not change, and vice versa for IBIs of anterior flexors and posterior extensors. We conclude that EMG activity patterns during paw-shaking are consistent with the proposed mechanism producing transient paw-shake-like bursting patterns found in our multistable HCO model. We suggest that the described asymmetry of paw-shaking responses could implicate a multifunctional CPG controlling both locomotion and paw-shaking.<\/jats:p>","DOI":"10.1371\/journal.pcbi.1009677","type":"journal-article","created":{"date-parts":[[2021,12,28]],"date-time":"2021-12-28T14:54:11Z","timestamp":1640703251000},"page":"e1009677","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":5,"title":["Asymmetric and transient properties of reciprocal activity of antagonists during the paw-shake response in the cat"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8323-079X","authenticated-orcid":true,"given":"Jessica R.","family":"Parker","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7800-6125","authenticated-orcid":true,"given":"Alexander N.","family":"Klishko","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0499-3890","authenticated-orcid":true,"given":"Boris I.","family":"Prilutsky","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1889-5397","authenticated-orcid":true,"given":"Gennady S.","family":"Cymbalyuk","sequence":"additional","affiliation":[]}],"member":"340","published-online":{"date-parts":[[2021,12,28]]},"reference":[{"issue":"Pt 20","key":"pcbi.1009677.ref001","article-title":"Expanding our horizons: central pattern generation in the context of complex activity sequences","volume":"222","author":"A. 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Koshland","year":"1989","journal-title":"J Neurophysiol"},{"issue":"6","key":"pcbi.1009677.ref038","doi-asserted-by":"crossref","first-page":"1874","DOI":"10.1152\/jn.1991.66.6.1874","article-title":"Fictive motor patterns in chronic spinal cats","volume":"66","author":"KG Pearson","year":"1991","journal-title":"J Neurophysiol"},{"issue":"1","key":"pcbi.1009677.ref039","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/s10827-008-0124-4","article-title":"Control of oscillation periods and phase durations in half-center central pattern generators: a comparative mechanistic analysis","volume":"27","author":"S Daun","year":"2009","journal-title":"Journal of computational neuroscience"},{"issue":"1","key":"pcbi.1009677.ref040","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1152\/jn.00550.2017","article-title":"State-dependent rhythmogenesis and frequency control in a half-center locomotor CPG","volume":"119","author":"J Ausborn","year":"2018","journal-title":"J 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Barbeau","year":"1987","journal-title":"Brain research"},{"issue":"1","key":"pcbi.1009677.ref047","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/0006-8993(90)90435-E","article-title":"The effects of serotonergic drugs on the locomotor pattern and on cutaneous reflexes of the adult chronic spinal cat","volume":"514","author":"H Barbeau","year":"1990","journal-title":"Brain research"},{"issue":"2","key":"pcbi.1009677.ref048","doi-asserted-by":"crossref","first-page":"1120","DOI":"10.1152\/jn.00216.2005","article-title":"Deletions of rhythmic motoneuron activity during fictive locomotion and scratch provide clues to the organization of the mammalian central pattern generator","volume":"94","author":"M Lafreniere-Roula","year":"2005","journal-title":"J Neurophysiol"},{"issue":"Pt 1","key":"pcbi.1009677.ref049","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1113\/jphysiol.2005.095505","article-title":"Parallel reflex pathways from flexor muscle afferents evoking 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