Nucleus Ambiguus (NA) Projections to Cardiac Ganglia Is Augmented Following Chronic Intermittent Hypoxia (CIH) in C57BL / 6J MICE

Abstract

Despite baroreflex sensitivity is reduced, the heart rate response to electrical stimulation of the cervical vagal nerve is significantly increased following CIH in mice (Lin et al. 2005). To elucidate the neural mechanism for such a paradoxical finding, we injected FG (i.p.) to label cardiac ganglia and DiI into the left NA to label vagal efferent, and then used a confocal microscope to examine NA axons and terminals in cardiac ganglia in room air (RA) and CIH conditions for 3 months (n=8/group). Our data indicated:1) Cardiac ganglia were widely distributed on the dorsal surface of atria. Though the total number of cardiac ganglia did not differ, the size of ganglia and the somata area of cardiac principal neurons (PNs) were both significantly decreased following CIH (p <0.01). 2) NA axons entered cardiac ganglia and innervated PNs with dense basket endings in both RA and CIH mice. The ratio of innervated and non-innervated PNs by DiI labeled axons in ganglia was not significantly different (RA: 50 ¡Ó 0.01 %; CIH: 49 ¡Ó 0.01%). In CIH mice, however, varicose endings around PNs appeared much swollen and the axonal varicose area around PNs was almost doubled (CIH: 163.1 ¡Ó 6.4£gm2; RA: 88 ¡Ó 3.9£gm2, n=100; p<0.001). We hypothesize that despite shrinkage of cardiac ganglia, enlarged synaptic connections of vagal efferent terminals with PNs may contribute to the increased vagal efferent control of heart rate following CIH. Since baroreflex sensitivity was reduced following CIH, we postulate that the remodeling of the other components (afferent and central) in brain-heart circuitry may contribute to attenuated baroreflex sensitivity. NIH RO1 HL-58727, HL-75034, AG21020.