Central pathways of pulmonary and lower airway vagal afferents

Abstract

Lung sensory receptors with afferent fibers coursing in the vagus nerves are broadly divided into three groups: slowly (SAR) and rapidly (RAR) adapting stretch receptors and bronchopulmonary C fibers. Central terminations of each group are found in largely nonoverlapping regions of the caudal half of the nucleus of the solitary tract (NTS). Second order neurons in the pathways from these receptors innervate neurons located in respiratory-related regions of the medulla, pons, and spinal cord. The relative ease of selective activation of SARs, and to a lesser extent RARs, has allowed for more complete physiological and morphological characterization of the second and higher order neurons in these pathways than for C fibers. A subset of NTS neurons receiving afferent input from SARs (termed pump or P-cells) mediates the Breuer-Hering reflex and inhibits neurons receiving afferent input from RARs. P-cells and second order neurons in the RAR pathway also provide inputs to regions of the ventrolateral medulla involved in control of respiratory motor pattern, i.e., regions containing a predominance of bulbospinal premotor neurons, as well as regions containing respiratory rhythm-generating neurons. Axon collaterals from both P-cells and RAR interneurons, and likely from NTS interneurons in the C-fiber pathway, project to the parabrachial pontine region where they may contribute to plasticity in respiratory control and integration of respiratory control with other systems, including those that provide for voluntary control of breathing, sleep-wake behavior, and emotions.

Inhibitory control of ascending glutamatergic projections to the lamprey respiratory rhythm generator

“…This interpretation is consistent with the functional organization of inhibitory modulation of NTS neurons in mammals (e.g. Miyazaki et al, 1999;Ezure and Tanaka, 2004;Kubin et al, 2006;Bailey et al, 2008). The OLA consists of three primary octavolateralis nuclei arranged dorsoventrally which receive multiple sensory inputs.…”

“…Accordingly, both the caudal ventral respiratory group and the caudal NTS neurons have been shown to be subject to a potent inhibitory control (see e.g. Miyazaki et al, 1999;Tonkovic-Capin et al, 2001Ezure and Tanaka, 2004;Kubin et al, 2006;Bailey et al, 2008).…”

Propofol enhances both tonic and phasic inhibitory currents in second-order neurons of the solitary tract nucleus (NTS)

“…Recorded neurons were located medial to the ST and within 200 µm rostral or caudal from obex -an area containing the densest synaptic terminals from aortic baroreceptors and substantial pulmonary afferent terminals (Mendelowitz et al, 1992;Doyle & Andresen, 2001;Kubin et al, 2006). Electrodes (3.5-4.5 MΩ) were visually guided to neurons using infrared illumination and differential interference contrast optics (40X water immersion lens) on an Axioskop-2 FS plus fixed stage microscope (Zeiss, Thornwood, NJ) with camera (Hamamatsu Photonic Systems, Bridgewater, NJ).…”

“…Common to most of these reflex pathways is the nucleus of the solitary tract (NTS), the site of central terminations of visceral cranial afferent nerves (including the vagus) from the cardiovascular, respiratory and gastrointestinal systems (Saper, 2002;Andresen et al, 2004;Travagli et al, 2006;Guyenet, 2006). Arterial baroreceptors and respiratory afferents terminate within medial portions of the caudal NTS and are a source of excitatory glutamatergic input onto second-order NTS neurons (Mendelowitz et al, 1992;Doyle & Andresen, 2001; Kubin et al, 2006). GABAergic transmission in NTS is also critical to normal cardiorespiratory reflex performance Kubin et al, 2006) as well as pathophysiological conditions (Urbanski & Sapru, 1988;Callera et al, 2000;Mei et al, 2003;Tolstykh et al, 2004).…”

“…Arterial baroreceptors and respiratory afferents terminate within medial portions of the caudal NTS and are a source of excitatory glutamatergic input onto second-order NTS neurons (Mendelowitz et al, 1992;Doyle & Andresen, 2001; Kubin et al, 2006). GABAergic transmission in NTS is also critical to normal cardiorespiratory reflex performance Kubin et al, 2006) as well as pathophysiological conditions (Urbanski & Sapru, 1988;Callera et al, 2000;Mei et al, 2003;Tolstykh et al, 2004).…”