In vivo modulation of vagal‐identified dorsal medullary neurones by activation of different 5‐Hydroxytryptamine₂ receptors in rats

Abstract

1 In in vivo experiments, DOI (a 5-HT 2 receptor agonist), MK-212 (a 5-HT 2C receptor agonist), and BW-723C86 (a 5-HT 2B receptor agonist) were applied by ionophoresis to neurones in the rat nucleus tractus solitarius (NTS) receiving vagal a erent input. 2 The majority of the putative`monosynaptically' vagal activated cells were inhibited by both MK-212 (4/6) and DOI (2/4), but una ected by . In contrast,`polysynaptically' activated NTS cells were excited by both BW-723C86 (13/19) and DOI (9/10). Inactive`intermediate' cells were inhibited by BW-723C86 (9/12), MK-212 (5/6) and DOI (3/4), whilst active cells of this group were excited by BW-723C86 (7/13) and DOI (5/5). 3 The selective 5-HT 2B receptor antagonist LY-202715 signi®cantly reduced the excitatory actions of BW-723C86 on`intermediate' and`polysynaptic' cells (13/13), but not the inhibitory e ects observed on inactive Group 2 cells (n=5) whereas the selective 5-HT 2C receptor antagonist RS-102221 reversed the inhibitory e ects of MK-212 and DOI on`monosynaptic and`intermediate' neurones. 4 Cardio-pulmonary a erent stimulation inhibited two of four putative`monosynaptically' activated calls and all four inactive intermediate cells. These were also inhibited by DOI and MK-212. In contrast, cardio-pulmonary a erents excited all ®ve active intermediate cells and all six putative`polysynaptically' activated NTS cells, while all were also previously excited by BW-723C86 and/or DOI. 5 In conclusion, these data demonstrate that neurones in the NTS are a ected di erently by 5-HT 2 receptor ligands, in regard of their vagal postsynaptic location, the type of cardio-pulmonary a erent they receive and the di erent 5-HT 2 receptors activated.

Molecular variability elicits a tunable switch with discrete neuromodulatory response phenotypes

“…However, it has been shown that AngII can exert both inhibitory and excitatory effects in the brainstem [93, 34], consistent with a distribution of phenotypes that traverses a separatrix. Our recent data suggest that phenotypic diversity in autonomic brainstem regions is highly plastic and is coordinated by anatomical connectivity [25], as found in other studies of neuromodulator response in in vivo [91]. Further, it has been shown that constraints at the gene regulatory level, mediated by particular combinations of transcription factors, coordinate physiological processes [94].…”

“…However, despite similar baseline firing rates, different conductance balances led to differential responsiveness to neuromodulation, as observed in experimental studies [8,91,92]. These divergent neuromodulation response profiles were associated with different pairwise molecular correlations, indicating that compensatory interactions support robust phenotypes [31].…”

Vagal afferent input alters the discharge of osmotic and ANG II-responsive median preoptic neurons projecting to the hypothalamic paraventricular nucleus

“…Within the ventrolateral medulla, previous studies have demonstrated that these neurons with ascending projections to the hypothalamus receive baroreceptor, cardiopulmonary, and vagal input (Li et al, 1992;Gieroba and Blessing, 1993;Stornetta et al, 1999;Verberne et al, 1999) and stimulation of the A1 area has been reported to increase cell discharge of MnPO-PVN neurons through the likely activation of α 1 -adrenoceptors (Tanaka et al, 1992). Alternatively, neurons of the nucleus tractus solitarius respond to cardiopulmonary and vagal afferent fiber activation (Raybould et al, 1988;McCann and Rogers, 1992;Hines et al, 1994;Sevoz-Couche et al, 2000), and orthodromic stimulation of this region typically produces an increase in MnPO cell discharge (Aradachi et al, 1996). Therefore, cardiopulmonary and/or vagal inputs may alter the excitability of MnPO neurons through mono-or polysynaptic pathways via the nucleus tractus solitarius or ventrolateral medulla.…”

Activation of 5‐HT1B and 5‐HT1D receptors in the rat nucleus tractus solitarius: opposing action on neurones that receive an excitatory vagal C‐fibre afferent input

“…At present, there is evidence suggesting that 5‐HT 3 ( Jeggo et al ., 2005 ) and 5‐HT 7 ( Kellett et al ., 2004 ), but probably not 5‐HT 1A ( Ramage and Mifflin, 1998 ), receptors in the NTS participate in the reflex pathways controlling cardiovascular reflexes. Furthermore, 5‐HT 2A/B and 5‐HT 2C receptors have also been found to affect NTS neurone activity and have opposing actions, excitation and inhibition, respectively ( Sévoz‐Couche et al ., 2000 ). However, central blockade of 5‐HT 2 receptors does not seem to interfere with cardiovascular ( Bogle et al ., 1990 ) or airway ( Bootle et al ., 1996 , 1998 ) reflexes mediated by the NTS.…”