Catecholaminergic Modulation of the Respiratory Rhythm Generator in the Isolated Brainstem—Spinal Cord Preparation from Neonatal Rat

Abstract

The hypothesized respiratory rhythm generator is located in the neonatal medulla and consists of pre-inspiratory (Pre-I) neurons in the parafacial respiratory group (pFRG) (Onimaru and Homma 2003) and inspiratory (I) neurons in the pre-Botzinger complex (PBC) (Smith, Ellenberger, Ballanyi, Richter and Feldman 1991). The Pre-I neurons are thought to trigger firing of I neurons (Onimaru, Arata and Homma 1997) which, in turn, send axons to the inspiratory motor neurons in the spinal cord. The respiratory rhythm generator is controlled in part by inputs from the nucleus tractus solitarii (NTS). The NTS is the main relay of the Hering-Breuer reflex. Moreover, the NTS receives direct projections from the cerebral cortex and the limbic system, including the insular cortex. The NTS contains catecholaminergic neurons that project to the respiratory rhythm generator in the rostral ventrolateral medulla (RVLM). In rats, adrenaline-containing neurons of the RVLM, namely the C1 group, are primarily unilaterally innervated by neurons in the NTS. Reis and colleagues suggested that these neurons synapsing in or projecting through the C1 area mediate the baroand cardiopulmonary mechanoreceptor reflex (Granata, Ruggiero, Park, Joh and Reis 1983). Dopamine antagonist administration in vivo attenuated ventilatory responses to hypoxia (Hsiao, Lahiri and Mokashi 1989), and direct dopamine application on the rat medulla–spinal cord preparation depressed respiratory frequency (Fujii, Umezawa and Arata 2004; 2006). Using the isolated medulla–spinal cord preparation and single-cell recordings, we investigated the cellular mechanisms of catecholaminergic respiratory regulation. Our data suggest respiratory depression by catecholamine is mediated primarily by effects on Pre-I neurons.