{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T05:43:56Z","timestamp":1792129436029,"version":"4.4.0"},"reference-count":34,"publisher":"American Physiological Society","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurophysiology"],"published-print":{"date-parts":[[2001,7,1]]},"abstract":"<jats:p>\n                    We used the testable predictions of mathematical models proposed by Butera et al. to evaluate cellular, synaptic, and population-level components of the hypothesis that respiratory rhythm in mammals is generated in vitro in the pre-B\u00f6tzinger complex (pre-B\u00f6tC) by a heterogeneous population of pacemaker neurons coupled by fast excitatory synapses. We prepared thin brain stem slices from neonatal rats that capture the pre-B\u00f6tC and maintain inspiratory-related motor activity in vitro. We recorded pacemaker neurons extracellularly and found: intrinsic bursting behavior that did not depend on Ca\n                    <jats:sup>2+<\/jats:sup>\n                    currents and persisted after blocking synaptic transmission; multistate behavior with transitions from quiescence to bursting and tonic spiking states as cellular excitability was increased via extracellular K\n                    <jats:sup>+<\/jats:sup>\n                    concentration ([K\n                    <jats:sup>+<\/jats:sup>\n                    ]\n                    <jats:sub>o<\/jats:sub>\n                    ); a monotonic increase in burst frequency and decrease in burst duration with increasing [K\n                    <jats:sup>+<\/jats:sup>\n                    ]\n                    <jats:sub>o<\/jats:sub>\n                    ; heterogeneity among different cells sampled; and an increase in inspiratory burst duration and decrease in burst frequency by excitatory synaptic coupling in the respiratory network. These data affirm the basis for the network model, which is composed of heterogeneous pacemaker cells having a voltage-dependent burst-generating mechanism dominated by persistent Na\n                    <jats:sup>+<\/jats:sup>\n                    current ( I\n                    <jats:sub>NaP<\/jats:sub>\n                    ) and excitatory synaptic coupling that synchronizes cell activity. We investigated population-level activity in the pre-B\u00f6tC using local \u201cmacropatch\u201d recordings and confirmed these model predictions: pre-B\u00f6tC activity preceded respiratory-related motor output by 100\u2013400 ms, consistent with a heterogeneous pacemaker-cell population generating inspiratory rhythm in the pre-B\u00f6tC; pre-B\u00f6tC population burst amplitude decreased monotonically with increasing [K\n                    <jats:sup>+<\/jats:sup>\n                    ]\n                    <jats:sub>o<\/jats:sub>\n                    (while frequency increased), which can be attributed to pacemaker cell properties; and burst amplitude fluctuated from cycle to cycle after decreasing bilateral synaptic coupling surgically as predicted from stability analyses of the model. We conclude that the pacemaker cell and network models explain features of inspiratory rhythm generation in vitro.\n                  <\/jats:p>","DOI":"10.1152\/jn.2001.86.1.59","type":"journal-article","created":{"date-parts":[[2017,12,21]],"date-time":"2017-12-21T05:54:56Z","timestamp":1513835696000},"page":"59-74","source":"Crossref","is-referenced-by-count":132,"title":["Models of Respiratory Rhythm Generation in the Pre-B\u00f6tzinger Complex. III. Experimental Tests of Model Predictions"],"prefix":"10.1152","volume":"86","author":[{"given":"Christopher A.","family":"Del Negro","sequence":"first","affiliation":[{"name":"Cellular and Systems Neurobiology Section, Laboratory of Neural Control, National Institute for Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892-4455; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheree M.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Cellular and Systems Neurobiology Section, Laboratory of Neural Control, National Institute for Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892-4455; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J.","family":"Butera","sequence":"additional","affiliation":[{"name":"School of Electrical and Computer Engineering, Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, Georgia 30332-0363"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey C.","family":"Smith","sequence":"additional","affiliation":[{"name":"Cellular and Systems Neurobiology Section, Laboratory of Neural Control, National Institute for Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892-4455; 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