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Volume 2 Supplement 1

Neural Control of Breathing

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Information processing at the nucleus tractus solitarii and respiratory rhythm generation

The nucleus tractus solitarii (NTS) relays information from primary visceral receptors to the central nervous system and is critically involved in the reflex control of autonomic functions. In the respiratory system, it is a part of so-called dorsal respiratory group (DRG) and plays an important role in the regulation of respiration. Although people have noticed that the NTS in general is not a simple relay nucleus but a place of information processing, such concept has not necessarily been realized in the respiratory system. Based on our recent data on NTS neurons, we now show some aspects of information processing taking place at the NTS. Inflation or deflation of the lungs evokes various respiratory reflexes by activating mainly two types of pulmonary stretch receptors. Slowly adapting receptors (SARs) are activated solely by inflation of the lungs and firmly involved in the Hering-Breuer reflex; on the other hand, rapidly adapting receptors (RARs) are activated by both inflation and deflation of the lungs but their functional role is still controversial. We aimed to determine the input-output properties of their second-order relay neurons (P-cells and RAR-cells, respectively) in the NTS. P-cells are key neurons of SAR-induced reflexes and have long been regarded as simple relay neurons; however, our experiments in the rat clearly showed that firing of P-cells (and RAR-cells) was modulated with central (not via afferents) respiratory rhythm, indicating that these second-order relay neurons are under influence of the respiratory center. In other words, the respiratory center gates the afferent inputs at the NTS before such inputs act on respiratory neurons that underlie the elaboration of various respiratory reflexes. Now P-cells and RAR-cells have been revealed to receive complex synaptic inputs involving glycinergic and GABAergic inhibitions and non-NMDA and NMDA glutamate receptor-mediated excitations [1]. Therefore, these "relay neurons" are crucially organized into the medullary respiratory network and can exert a phasic influence on the central rhythm generating mechanisms even without receiving afferent inputs from SARs and RARs.

RAR-cells respond characteristically to lung deflation but do not necessarily respond to lung inflation. This is somewhat peculiar since RAR afferents respond to both inflation and deflation of the lungs. This suggests the possibility that lung inflation that activates RARs on one hand suppresses RAR-cell firing on the other hand. Recently we found evidence that this suppression is caused by synaptic inhibition of RAR-cells from P-cells (P-R linkage) [2]. This implies that some P-cells are inhibitory and that the SAR and RAR systems are not independent but work cooperatively to evoke respiratory reflexes. On the assumption that RAR pathways mediate inspiratory facilitation, this P-R linkage seems to explain the neuronal mechanisms underlying the Hering-Breuer inflation and deflation reflexes. That is, inflation of the lungs activates preferentially SAR pathways by inhibiting RAR pathways and deflation of the lungs activates RAR pathways.

In the NTS area, ie in the DRG, we identified a novel group of inspiratory neurons, which receive monosynaptic inputs from low-threshold vagal afferents and respond to lung deflation [3]. It is quite possible that RAR afferents innervate these deflation-sensitive inspiratory neurons (tentatively termed Iγ neurons). Until now we have no suitable answer to the question why two types of inspiratory (Iα and Iβ) neurons exist in the DRG. The fact that DRG inspiratory neurons are classified into at least three groups, Iα, Iβ and Iγ neurons, has made the situation more complex but provides new insight into the organization and role of the NTS, which integrates afferent inputs and the central respiratory rhythm.


  1. Miyazaki M, Tanaka I, Ezure K: Excitatory and inhibitory inputs shape the discharge pattern of pump neurons of the nucleus tractus solitarii in the rat. Exp Brain Res. 1999, 129: 191-200. 10.1007/s002210050889.

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  2. Ezure K, Tanaka I: Lung inflation inhibits rapidly adapting receptor relay neurons in the rat. Neuroreport. 2000, 11: 1709-1712. 10.1097/00001756-200006050-00023.

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  3. Ezure K, Tanaka I: Identification of deflation-sensitive inspiratory neurons in the dorsal respiratory group of the rat. Brain Res. 2000, 883: 22-30. 10.1016/S0006-8993(00)02871-7.

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Ezure, K. Information processing at the nucleus tractus solitarii and respiratory rhythm generation. Respir Res 2 (Suppl 1), 2.3 (2001).

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