Pulmonary stretch receptor modulation of synaptic inhibition shapes the discharge pattern of respiratory premotor neurons

Abstract

Many studies focus on the mechanisms of respiratory rhythm generation through neuronal interactions in the preBötzinger and Bötzinger complex area. There is limited insight into how the varied discharge patterns of propriobulbar, rhythm generating neurons are integrated to generate the slowly augmenting and decrementing discharge patterns observed in respiratory premotor neurons. Neuronal discharge patterns were obtained, in vivo, from inspiratory (I) and expiratory (E) premotor neurons in the ventral respiratory group of adult, anesthetized and vagotomized canines. Electrical activation of vagal afferents was used to produce pulmonary stretch receptor (PSR), step-input patterns, throughout or within either the I- or E-phase. PSR inputs decreased the discharge pattern slopes of augmenting and decrementing E-neurons and increased the slopes of augmenting and decrementing I-neurons. PSR inputs that were applied only for part of the phase acutely changed the discharge pattern to the trajectory associated with those PSR throughout-phase inputs, but the pattern returned immediately to the original trajectory after the PSR input terminated. These types of responses can be reproduced with high fidelity by a mathematical model based on reciprocal inhibition between augmenting and decrementing neurons of the same respiratory phase. Best fit is achieved when PSR inputs solely modulate the strength of the synaptic inhibition of decrementing neurons by augmenting neurons at the presynaptic level. Leaky integrator functions are not necessary to generate the gradually augmenting and decrementing patterns. This model offers a novel and different mechanistic way to conceptualize the generation and PSR control of respiratory discharge patterns.