Release of ATP and glutamate in the nucleus tractus solitarii mediate pulmonary stretch receptor (Breuer–Hering) reflex pathway

Abstract

The Breuer-Hering inflation reflex is initiated by activation of the slowly adapting pulmonary stretch receptor afferents (SARs), which monosynaptically activate second-order relay neurones in the dorsal medullary nucleus of the solitary tract (NTS). Here we demonstrate that during lung inflation SARs release both ATP and glutamate from their central terminals to activate these NTS neurones. In anaesthetized and artificially ventilated rats, ATP-and glutamate-selective microelectrode biosensors placed in the NTS detected rhythmic release of both transmitters phase-locked to lung inflation. This release of ATP and glutamate was independent of the centrally generated respiratory rhythm and could be reversibly abolished during the blockade of the afferent transmission in the vagus nerve by topical application of local anaesthetic. Microionophoretic application of ATP increased the activity of all tested NTS second-order relay neurones which receive monosynaptic inputs from the SARs. Unilateral microinjection of ATP into the NTS site where pulmonary stretch receptor afferents terminate produced central apnoea, mimicking the effect of lung inflation. Application of P2 and glutamate receptor antagonists (pyridoxal-5 -phosphate-6-azophenyl-2 ,4 -disulphonic acid, suramin and kynurenic acid) significantly decreased baseline lung inflation-induced firing of the second-order relay neurones. These data demonstrate that ATP and glutamate are released in the NTS from the central terminals of the lung stretch receptor afferents, activate the second-order relay neurones and hence mediate the key respiratory reflex -the Breuer-Hering inflation reflex.

Rapid changes in extracellular glutamate induced by natural arousing stimuli and intravenous cocaine in the nucleus accumbens shell and core

“…Moreover, as confirmed by postrecording in vitro calibrations, these sensors remained Glu sensitive and selective after the in vivo experiment. Consistent with previous reports with the same (Behrend et al 2009;John et al 2008) or different (Dash et al 2009;Gourine et al 2008;Hascup et al 2010;Rutherford et al 2007) designs of Glu sensors, postrecording Glu sensitivity of our sensors dropped almost twofold, reflecting mainly contamination of their active area by brain substances, most notably by albumin. Taking into account all these factors, it was reasonable to assume that the stimulusinduced changes in oxidation currents detected in the in vivo experiment reflect fluctuations in extracellular Glu levels.…”

“…Relatively large fluctuations in [Glu] (ϳ1-10 M) were also reported in the cortex after spontaneous transitions within the sleep-wake cycle (Dash et al 2009;John et al 2008;Naylor et al 2011) and in the NAc shell after a systemic injection of MK-801, a noncompetitive NMDA antagonist (Uslaner et al 2011). In contrast, with simultaneous two-sensor (Glu-Glu 0 ) recordings, only ϳ25-35 nM phasic increases in [Glu] were detected during breathing in the medulla of anesthetized rats (Gourine at al. 2008).…”

Combined electrophysiological and biosensor approaches to study purinergic regulation of epileptiform activity in cortical tissue

“…Such delays do not detract from the ability to correlate, in our case, purine release with ongoing synaptic or physiological activity. For example the in vivo ATP release from sensory afferents was shown to be phase locked to respiratory rhythm (cycle period of about 1s) (Gourine et al, 2008).…”

Mecanismos purinérgicos no bulbo ventrolateral rostral modulam respostas cardiovasculares e respiratórias promovidas pela ativação dos quimiorreceptores centrais e periféricos.

“…bradycardia, hypertension and tachypnoea) to peripheral chemoreceptor activation Antunes et al 2005a). Purinergic signalling also contributes to pulmonary stretch receptor-mediated activation of second-order relay neurons in the NTS to control inspiration (Gourine et al 2008). Consistent with the possibility that purinergic signalling in the cNTS contributes to cardiorespiratory control, we show that ATP injections into this region increased cardiorespiratory activity.…”