Cardiac vagal preganglionic neurons (CVPN) are found predominantly in the nucleus ambiguus (NA) as well as dorsal motor nucleus of the vagus (DMNV) and in the intermediate zone (IZ) between these two nuclei [1–3]. Activation of CVPN has negative chronotropic, dromotropic and ionotropic effects on the heart [4–6] and the activity of these neurons is increased in response to baroreceptor stimulation [7–9] and inhibited during inspiration [10, 11].
Surprisingly little is known about the functional significance of inputs to CVPN mediated by either ionotropic or g-protein coupled receptors (GPCR). CVPN receive substantial inputs from ionotropic receptors. Microinjection of the GABAA receptor antagonist bicuculline into the NA evokes a profound decrease in HR  demonstrating that there is a large GABAergic input to CVPN that plays a role in setting the tonic level of heart rate (HR). GABAergic inputs also appear to mediate the inspiratory related inhibition of CVPN and may play a role in generating respiratory sinus arrhythmia (RSA) . Although glycine evokes tachycardia when injected unilaterally into the NA , the role of glycinergic inputs in both the tonic and reflex control of cardiac vagal outflow have not been systematically explored. Glutamatergic inputs, conversely, mediate baroreceptor dependent excitation of CVPN [7, 15–17], however the glutamate receptor subtype(s) involved has yet to be determined.
The influence some GPCR have in regulating CVPN has been determined. For example, activation of serotonin-1a/7, dopamine, μ-opioid or neurokinin-1 receptors within the NA decreases HR whereas activation of opioid-receptor like receptor-1 increases HR, demonstrating that activation of some GPCR can differentially alter the tonic level of HR [18–21]. The role of these GPCR, or for that matter others, however, in the reflex modulation of HR is not well understood. Systemic activation of serotonin-1A (5-HT1A) receptors potentiates baroreflex mediated bradycardia [22, 23]. Central administration of the selective 5-HT1A antagonist, WAY-100635, attenuates baroreflex sensitivity suggesting a pivotal role for 5-HT1A receptors in the maintenance of reflex cardiac vagal outflow . Furthermore, 5-HT1A receptor modulation of reflex cardiac vagal outflow is absent in the flinders sensitive line rat, an animal model of depression, which exhibits reduced BRS , thus highlighting the clinical importance of functional 5-HT1A receptor control of cardiac vagal outflow.
How activation of 5-HT1A receptors produces bradycardia and enhances baroreflex bradycardia is unknown. Speculation suggests that as the 5-HT1A receptor is an inhibitory GPCR, the mechanism must involve an interaction with inhibitory ionotropic inputs to CVPN . In keeping with this hypothesis, application of 8-OH-DPAT in vitro attenuates presynaptic GABAergic and glycinergic inputs to CVPN [26, 27]; however the functional significance of these inputs is unknown. Whether or not the effects of 5-HT1A activation on HR or BRS are mediated by GABAergic and/or glycinergic inhibition of CVPN in the ventrolateral medulla has not been investigated in vivo.
The initial aim of this study was to assess comprehensively, in the rat, the roles of GABAA, strychnine-sensitive glycine and NMDA and AMPA receptors within regions of the medulla containing CVPN in the tonic and reflex control of HR. Secondly, we investigated if activation of the 5-HT1A receptor evoked bradycardia and potentiation of baroreflex bradycardia was dependent upon GABAergic or glycinergic neurotransmission to CVPN.