Role of serotonergic input to the ventrolateral medulla in expression of the 10-Hz sympathetic nerve rhythm

Abstract

We studied the changes in inferior cardiac sympathetic nerve discharge (SND) produced by unilateral microinjections of 5-hydroxytryptamine (5-HT) receptor agonists and antagonists into the ventrolateral medulla (VLM) of urethane-anesthetized, baroreceptor-denervated cats. Microinjection of the 5-HT2 receptor antagonist LY-53857 (10 mM) into either the rostral or caudal VLM significantly reduced (P < or = 0.05) the 10-Hz rhythmic component of basal SND without affecting its lower-frequency, aperiodic component. The selective depression of 10-Hz power was accompanied by a statistically significant decrease in mean arterial pressure (MAP). Microinjection of LY-53857 into the VLM also attenuated the increase in 10-Hz power that followed tetanic stimulation of depressor sites in the caudal medullary raphé nuclei. Microinjection of the 5-HT2 receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)2-amino-propane (DOI; 10 microM) into the VLM selectively enhanced 10-Hz SND, and intravenous DOI (1 mg/kg) partially reversed the reduction in 10-Hz SND produced by 5-HT2 receptor blockade in the VLM. Microinjection of the 5-HT1A receptor agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OHDPAT; 10 mM), into either the rostral or caudal VLM also selectively attenuated 10-Hz SND and significantly reduced MAP. The reduction in 10-Hz SND produced by 8-OHDPAT was partially reversed by intravenous WAY-100635 (1 mg/kg), which selectively blocks 5-HT1A receptors. These results support the view that serotonergic inputs to the VLM play an important role in expression of the 10-Hz rhythm in SND.

What can we learn about neural control of the cardiovascular system by studying rhythms in sympathetic nerve activity?

“…Barman and Gebber and their colleagues have used several approaches in anaesthetized cats to identify central neurons that generate and/or transmit rhythmic activity to the spinal intermediolateral cell column that contains the cell bodies of preganglionic neurons. These include 1) applying correlation analyses (spike-triggered averaging and coherence analysis) to the simultaneously recorded activity of individual brainstem neurons and sympathetic nerves, 2) microinjecting agonists or antagonists of putative central neurotransmitters, including glutamate, GABA, serotonin, catecholamines, into different medullary and pontine regions to characterize changes in SNA rhythmicity, and 3) using the technique of antidromic activation to determine interconnections of medullary neurons and projections of brainstem neurons to the IML (Barman and Gebber, 1992, 1993, 1997, 1998, 2007; Barman et al, 1994, 1997, 1999, 2002, 2005; Orer et al, 1999, 2008). …”

The Influence of Pc6 on Cardiovascular Disorders: A Review of Central Neural Mechanisms

“…It is therefore likely that the medullary raphe nuclei, particularly the nucleus raphe pallidus, process somatic signals during acupuncture and participate in acupuncture-mediated modulation effects on cardiovascular function by an opioid or serotonergic mechanism 2532 The midline medulla oblongata modulates sympathetic outflow and cardiovascular responses by means of the RVLM,33–35 and the raphe nuclei directly project to the RVLM 36. Opioids and 5-HT function as important neurotransmitters in this region,37 38 and during electroacupuncture, serotonergic neurons mediate the input from the nucleus raphe pallidus to the RVLM to inhibit the sympathetic outflow 31…”

Responses of opioid and serotonin containing medullary raphe neurons to electroacupuncture

“…The midline medulla oblongata, including, in part, the nucleus raphe obscurus (NRO), nucleus raphe magnus (NRM) and nucleus raphe pallidus (NRP), modulates sympathetic outflow and cardiovascular responses through an influence on the rVLM (Coleman and Dampney, 1995; Bago et al, 2002; Orer et al, 2008). There are direct neuronal projections from the raphe nuclei to the rVLM (Bago et al, 2002).…”