The long-term objective of this proposal is to contribute to the understanding of central respiratory chemoreceptor function and development in the larval Rana catesbeiana brainstem. One unresolved issue that prevents further understanding of central respiratory chemoreceptors is the ability to distinguish between chemoreceptors that are respiratory from non-respiratory. Therefore, specific aim one includes the ontogenetic characterization of central candidate chemoreceptors in the larval Rana catesbeiana brainstem using the following criteria: 1) cells must be localized in a region known to contribute to ventilatory control 2) cells must respond to alterations in CO2/H+ level with an increase in firing rate 3) cells must be intrinsically chemosensitive Since there is increasing evidence of pHi as the primary stimulus in chemosensitive cells, pHi regulation in chemosensitive and non-chemosensitive sites will also be monitored using the pH-sensitive dye BCECF. The second specific aim involves focally stimulating chemosensitive sites that elicit a whole nerve respiratory response while monitoring changes in pHi. This will allow the quantification of the contribution of these sites to respiration and establish if there is a direct role of pHi on ventilation. Techniques include whole cell perforated recordings, whole nerve respiratory output recordings, focal applications, and fluorescence microscopy. Sudden Infant Death Syndrome (SIDS) is the most common cause of death in infants between the ages of one month and one year (Kinney 2002). Since there is increasing evidence suggesting that SIDS may involve abnormalities in the neurological control of breathing, central chemoreceptor location and mechanisms of action are of great interest and may provide important insight into the pathophysiology of SIDS. ? ? ?
