Cardiac baroreflex facilitation evoked by hypothalamus and prefrontal cortex stimulation: role of the nucleus tractus solitarius 5-HT_2Areceptors

Abstract

We previously showed that serotonin (5-HT2) receptor activation in the nucleus of the tractus solitarius (NTS) produced hypotension, bradycardia, and facilitation of the baroreflex bradycardia. Activation of the preoptic area (POA) of the hypothalamus, which is involved in shock-evoked passive behaviors, induces similar modifications. In addition, previous studies showed that blockade of the infralimbic (IL) part of the medial prefrontal cortex, which sends projections to POA, produced an inhibitory influence on the baroreflex cardiac response. Thus, to assess the possible implication of NTS 5-HT2 receptors in passive cardiovascular responses, we analyzed in anesthetized rats the effects of NTS inhibition and NTS 5-HT2 receptor blockade on the cardiovascular modifications induced by chemical (0.3 M D,L-homocysteic acid) and electrical (50 Hz, 150-200 microA) stimulation of IL or POA. Intra-NTS microinjections of muscimol, a GABAA receptor agonist, prevented the decreases in blood pressure and heart rate normally evoked by IL or POA activation. In addition, we found that intra-NTS microinjection of R(+)-alpha-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenylethyl)]-4-piperidine-methanol, a specific 5-HT2A receptor antagonist, did not affect the decreases in cardiovascular baseline parameters induced by IL or POA stimulation but prevented the facilitation of the aortic baroreflex bradycardia normally observed during IL (+65 and +60%) or POA (+70 and +69%) electrical and chemical stimulation, respectively. These results show that NTS 5-HT2A receptors play a key role in the enhancement of the cardiac response of the baroreflex but not in the changes in basal heart rate and blood pressure induced by IL or POA stimulation.

Neural connection supporting endogenous 5-hydroxytryptamine influence on autonomic activity in medial prefrontal cortex

“…In addition, the PL/IL labeling, as was observed in the present study, was localized to lamina V ( Fig. 1D-F), occupying the cortical area that fits quite well the loci of electrical or chemical stimulation that evoked altered gastric motility, heart rate and blood pressure (Hurley-Gius and Neafsey, 1986;Sevoz-Couche et al, 2006;Hassan et al 2013 and. The retrograde labeling in M1 and M2 suggests that these corticomotor areas project to DVC.…”

“…In addition, mPFC is actively involved in autonomic regulation, as is evidenced by the decreased gastric motility, hypotension and bradycardia following stimulation of the prelimbic (PrL) and infralimbic cortices (IL) (Hurley-Gius and Neafsey, 1986;Heidbreder and Groenewegen, 2003;Sevoz-Couche et al, 2006;Hassan et al, 2013), the two important subdivisions of mPFC. Previous studies indicated that this autonomic effect might be mediated through divergent pathways including mPFC projections to brain stem dorsal vagal complex (DVC), which is composed of nucleus of solitary tract (Sol), the dorsal motor nucleus of vagus (DMV) and area postrema, either directly or indirectly via relay of such structures as amygdala and hypothalamus (Saper, 2004;Gabbott et al, 2005;Sevoz-Couche et al, 2006;Mussa and Verberne, 2013). Thus, DVC plays a pivotal role in mediating descending control of autonomic activities.…”

Voluntarily Produced Increases in Heart Rate Variability Modulate Autonomic Effects of Endotoxin Induced Systemic Inflammation: An Exploratory Study

“…There is evidence that the same brain stem nuclei [e.g. the nucleus tractus solitarius (Sevoz-Couche et al 2006) regulate both the inflammatory and baroreflex systems. Among people who are gravely ill, reduced HRV is a predictor of death (Bluzaite et al 2006;Chan 2008;Christensen 2003;Politano et al 2008).…”

Medial Prefrontal Cortex

“…Although the characteristic neurochemical, ultrastructural and functional properties of target neurons in the NTS and VLM receiving synaptic input from IL cortex need to be fully defined in future studies (Resstel and Corrêa, 2006a,b;Sevoz-Couche et al, 2006), one important question emerges from the present data: 'What are the functional implications of the comparatively modest IL input to THϩ neurons in both the NTS and rVLM? ' Immunocytochemical evidence indicates that the descending projections from IL cortex would provide 'excitatory' glutamatergic input to the dendritic shafts and spines of neurochemically diverse target neurons in both NTS and rVLM (Torrealba and Müller, 1999).…”