A Novel Functional Neuron Group for Respiratory Rhythm Generation in the Ventral Medulla

Abstract

We visualized respiratory neuron activity covering the entire ventral medulla using optical recordings in a newborn rat brainstem-spinal cord preparation stained with voltage-sensitive dye. We measured optical signals from several seconds before to several seconds after the inspiratory phase using the inspiratory motor nerve discharge as the trigger signal; we averaged the optical signals of 50-150 respiratory cycles to obtain an optical image correlating particularly to inspiratory activity. The optical images we obtained from the ventral approach indicated that neuron activity first appeared during the respiratory cycle in the limited region of the rostral ventrolateral medulla (RVLM), preceding the onset of inspiratory activity by approximately 500 msec. During the inspiratory phase, plateau activity appeared in the more caudal ventrolateral medulla at the level of the most rostral roots of the XIIth nerve. Comparison with electrophysiological recordings from respiratory neurons in the RVLM suggested that the optical signals preceding the inspiratory burst reflect preinspiratory neuron activity in this area. This RVLM area was determined to be ventrolateral to the facial nucleus and close to the ventral surface. We referred to this functional neuron group as the para-facial respiratory group (pFRG). Partial, bilateral electrical lesioning of the pFRG significantly reduced the respiratory frequency, together with changes in the spatiotemporal pattern of respiratory neuron activity. Our findings suggest that the pFRG comprises a neuronal population that is involved in the primary respiratory rhythm generation in the rostrocaudally extending respiratory neuron network of the medulla.

Large lesions in the pre-Bötzinger complex area eliminate eupneic respiratory rhythm in awake goats

“…These data provide evidence of a second rhythm generator (expiratory), which is only expressed with depression of the inspiratory rhythm generator. This expiratory rhythm generator is rostral to the pre-BötzC area ventrolateral to the rostral Bötzinger complex and/or in the parafacial region (4,8,14,17). In goats during the tachypneic period following IA injections, rhythmic abdominal muscle activity was clearly present, and it was characteristically 180°o ut of phase with diaphragm activity.…”

“…In addition, in vivo studies in anesthetized or decerebrate cats or rats demonstrate that lesioning of the pre-BötzC results in transient (24) or irreversible (7, 10, 18) elimination of eupneic respiratory activity. Further demonstrating the importance of the pre-BötzC in control of breathing was a study showing that Ͼ80% destruction of neurokinin-1 receptor (NK1R)-expressing neurons in the pre-BötzC resulted in an ataxic breathing pattern and hypoventilation in awake rats (6).Recently, it has been proposed that, within the medulla, there are two respiratory rhythm generators, which are mutually inhibitory and each capable of generating a rhythm under different conditions: one is an inspiratory generator composed of pre-BötzC inspiratory neurons, and the second is an expiratory generator composed of preinspiratory (pre-I) neurons ventrolateral to the rostral Bötzinger complex (4,8,14,17). Supposedly, the pre-BötzC rhythm generator is normally dominant, and it inhibits the rostral pre-I neurons (14), which initiate rhythmic abdominal muscle contraction when preBötzC inspiratory neuronal activity is depressed (4, 8).…”

“…Recently, it has been proposed that, within the medulla, there are two respiratory rhythm generators, which are mutually inhibitory and each capable of generating a rhythm under different conditions: one is an inspiratory generator composed of pre-BötzC inspiratory neurons, and the second is an expiratory generator composed of preinspiratory (pre-I) neurons ventrolateral to the rostral Bötzinger complex (4,8,14,17). Supposedly, the pre-BötzC rhythm generator is normally dominant, and it inhibits the rostral pre-I neurons (14), which initiate rhythmic abdominal muscle contraction when preBötzC inspiratory neuronal activity is depressed (4,8).…”

Rapid and Precise Control of Sniffing During Olfactory Discrimination in Rats

“…Respiration is proximally controlled by central pattern generator (CPG) nuclei in the brain stem (Feldman and Ellenberger 1988;Mellen et al 2003;Onimaru and Homma 2003), which integrate a variety of descending inputs from cortical and subcortical structures (Gaytan and Pasaro 1998). Studies in anesthetized animals and in vitro preparations have shown that respiratory patterns can be finely controlled by afferent input (Arata et al 2000;Morris et al 2003).…”

A vibrating microtome attachment for cutting brain slice preparations at reproducible compound angles relative to the midline

“…Both regions are rich in respirationmodulated neurons, and have been proposed as playing a critical role in respiratory rhythm generation (Janczewski and Feldman, 2006;Onimaru et al, 1988;Onimaru et al, 2006;Smith et al, 1991). Low spatial resolution optical recordings from the en bloc brainstem spinal cord preparation (Onimaru and Homma, 2003) indicated that the pFRG lay lateral to the preBötC, and provided a starting point for the parametrization of a sagittal slab preparation. Parameters that exposed both networks were arrived at iteratively (across many preparations) by adjusting ventrodorsal and rostrocaudal tilt, and mediolateral level of section so as to isolate a preparation that displayed Ca ++ signals at the level of the pFRG and preBötC, and that generated a stable respiratory rhythm at physiological…”