The Rostral Portion of the Ventral Medulla or Rvm Comprises Several Groups of Neurons That Are Thought to Be Involved in Cardio-res-

THE ROSTRAL PORTION OF THE VENTRAL MEDULLA OR RVM COMPRISES SEVERAL GROUPS OF NEURONS THAT ARE THOUGHT TO BE INVOLVED IN CARDIO-RESPIRATORY CONTROL, including the retrotrapezoid nucleus (RTN), portions of the nucleus paragigantocellularis lateralis (PGCL), the parapyramidal region, and the caudal raphé.1 The RVM has anatomic connections to the dorsal and ventral respiratory groups,2 the intermediolateral cell column,3 and many other sites in the brainstem that are involved in autonomic control.4-6 Caudal raphé regions, including the parapyramidal area, are also important for thermoregulation and the modulation of sensory input.7-8 In addition, neurons in this region, particularly those in the PGCL, provide inputs to the locus coeruleus9 and thus provide a possible substrate for a role in modulation of arousal tone. Some neurons in the RVM exhibit a respiratory related rhythm and increase their firing rate in response to CO2. For example, neurons in the RTN of cats and rats exhibit a respiratory related rhythm,10-11 some of which increase their firing rate in response to increased inspired [CO2].12 Recently, experiments in conscious, unanesthetized rats have shown that CO2 microdialysis into the RTN increases breathing during wakefulness but not during sleep.13 Small chemical lesions in the RVM of anesthetized or decerebrate cats and rats inhibit resting ventilation and also reduce the response to systemic hypercapnia.14-16 In contrast, chemical lesions in the RVM in the unanesthetized rat do not have any major effects on resting ventilation but reduce the ventilatory response to systemic hypercapnia by 39%.16 The human arcuate nucleus, a diffuse thin layer of cells on the ventral surface of the brainstem, lies within the rostral ventral medulla (RVM).17-19 A major recent advance in our understanding of the pathogenesis of SIDS has been the findings of abnormalities in the arcuate nucleus and the caudal raphé in infants who died of SIDS. Initially, a small subset of SIDS infants was found to have severe hypoplasia of the arcuate nucleus.17 Subsequently, the brainstems of SIDS victims were found to have decreases in muscarinic20 and kainate21 binding in the arcuate nucleus, as well as a widespread reduction in 3H-LSD binding in other parts of the RVM including the caudal raphé and adjacent serotonergic regions, including the PGCL.22 This information led to the general hypothesis that abnormalities in this region of the brainstem may contribute to the etiology of a subset of SIDS by interfering with normal protective or defense responses, including arousal from sleep, to stimuli such as hypoxia, hypercapnia, and reflex apnea. There is limited information about the role of these brainstem regions in the newborn animal. We have recently demonstrated that both electrolytic lesions and dialysis of muscimol, a GABAA agonist, in the RVM of decerebrate piglets reduce baseline phrenic nerve activity and the response to systemic hypercapnia.1 Also, cooling of the surface of the RVM in anesthetized piglets interferes with the interaction of hypercapnia and reflex respiratory inhibition caused by stimulation of the larynx.23 Few exper-