Neurokinin-1 Receptors Modulate the Excitability of Expiratory Neurons in the Ventral Respiratory Group

Abstract

We studied the role of neurokinin-1 receptors (NK1-R) on the excitability of expiratory (E) neurons (tonic discharge, ETONIC; augmenting, EAUG; decrementing, EDEC) throughout the ventral respiratory group, including Bötzinger Complex (BötC) using extracellular single-unit recording combined with pressurized picoejection in decerebrate, arterially perfused juvenile rats. Responses evoked by picoejection of the NK1-R agonist, [Sar9-Met(O2)11]-substance P (SSP) were determined before and after the selective NK1-R antagonist, CP99,994. SSP excited 20 of 35 expiratory neurons by increasing the number of action potentials per burst (+33.7 ± 6.5% of control), burst duration (+20.6 ± 7.9% of control), and peak firing frequency (+16.2 ± 4.8% of control; means ± SE). Pretreatment with CP99,994 completely blocked SSP-evoked excitation in a subset of neurons tested, supporting the notion that SSP excitation was mediated through NK1-R activation. Because we had previously shown that EAUG neurons were crucial to locomotor-respiratory coupling (LRC), we reasoned that blockade of NK1-R would alter LRC by preventing somatic-evoked excitation of EAUG neurons. Blockade of NK1-Rs by CP99,994 in the BötC severely disrupted LRC and prevented somatic-evoked excitation of EAUG neurons. These findings demonstrate that LRC is dependent on endogenous SP release acting via NK1-Rs on EAUG neurons of the BötC. Taken together with our earlier finding that inspiratory off-switching by the Hering-Breuer Reflex requires endogenous activation of NK1-Rs through activation of NK1-Rs on EDEC neurons, we suggest that endogenous release of substance P in the BötC provides a reflex pathway-dependent mechanism to selectively modulate respiratory rhythm.