@article {Pagliardini9575, author = {Silvia Pagliardini and Jun Ren and John J. Greer}, title = {Ontogeny of the Pre-B{\"o}tzinger Complex in Perinatal Rats}, volume = {23}, number = {29}, pages = {9575--9584}, year = {2003}, doi = {10.1523/JNEUROSCI.23-29-09575.2003}, publisher = {Society for Neuroscience}, abstract = {The aim of this study was to provide a systematic examination of the ontogenesis of the mammalian respiratory rhythm generating center, the pre-B{\"o}tzinger complex (pre-B{\"o}tC). A combination of immunohistochemical markers and electrophysiological recordings was used to determine the time of inception of the pre-B{\"o}tC and the developmental changes during the perinatal period in rats spanning from embryonic day 15 (E15) to postnatal day 7. The first clear indication of neurons immunopositive for neurokinin-1 receptors (NK1Rs) and somatostatin expression, two proposed markers for pre-B{\"o}tC neurons, was at \~{}E17. Birth dating of neurons in the ventrolateral medulla using 5-bromo-2'-deoxyuridine demonstrated that NK1R-positive neurons populating the area of the pre-B{\"o}tC during late E16-E18 are born at E12.5-E13.5, \~{}2 d later than adjacent NK1R-positive neurons in the ventrolateral medulla. Extracellular recordings of neuronal populations within the pre-B{\"o}tC of perinatal medullary slice preparations demonstrated that the onset of rhythmical respiratory discharge commences at \~{}E17. Application of substance P, a ligand for NK1R receptors, to the media bathing E17 medullary slice and brainstem-spinal cord preparations resulted in a marked increase in respiratory frequency. These data provide insights into the ontogeny of the pre-B{\"o}tC, giving fundamental information on the genesis, settlement, and inception of rhythmic activity within the group of neurons proposed to be responsible for the respiratory rhythm generation. Furthermore, this provides the foundation for further analyses of cell lineage, the transcriptional control of respiratory neuronal development, and electrophysiological and pharmacological properties of the pre-B{\"o}tC during the prenatal period.}, issn = {0270-6474}, URL = {https://www.jneurosci.org/content/23/29/9575}, eprint = {https://www.jneurosci.org/content/23/29/9575.full.pdf}, journal = {Journal of Neuroscience} }