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Modulation of bulbospinal rostral ventral lateral medulla neurons by hypoxia/hypercapnia but not medullary respiratory activity.

ABSTRACT: Although sympathetic vasomotor discharge has respiratory modulation, the site(s) responsible for this cardiorespiratory interaction is unknown. One likely source for this coupling is the rostral ventral lateral medulla (RVLM), where presympathetic neurons originate in close apposition to respiratory neurons. The current study tested the hypothesis that RVLM bulbospinal neurons are modulated by medullary respiratory network activity using whole-cell patch-clamp electrophysiological recordings of RVLM neurons while simultaneously recording fictive respiratory bursting activity from the hypoglossal rootlet. Additionally, we examined whether challenges to cardiorespiratory function, mainly hypoxia/hypercapnia, alter the activity of bulbospinal neurons and, secondarily, whether changes in synaptic input mediate these responses. Surprisingly, our results indicate that inspiratory-related activity did not modulate glutamatergic, ?-aminobutyric acid-ergic, or glycinergic synaptic events or spontaneous action potential firing in these RVLM neurons. However, hypoxia/hypercapnia reversibly decreased the frequency of ?-aminobutyric acid and glycine inhibitory postsynaptic currents. Glycinergic inhibitory postsynaptic current frequency was depressed from the fifth through the 10th minute, whereas the depression of ?-aminobutyric acid-ergic events became significant only at the 10th minute of hypoxia/hypercapnia. On the basis of spontaneous firing activity, there were 2 populations of RVLM bulbospinal neurons. The firing frequency of low-discharging RVLM neurons was facilitated by hypoxia/hypercapnia, and this increase depended on reduced inhibitory neurotransmission. The firing frequency in RVLM neurons with high-discharge rates was inhibited, independent of synaptic input, by hypoxia/hypercapnia. This article demonstrates that sympathetic-respiratory coupling is not active in the neonatal brain stem slice, and reductions in inhibitory neurotransmission to low spontaneously active bulbospinal RVLM neurons are responsible for hypoxia/hypercapnia-elicited increases in activity.

SUBMITTER: Boychuk CR

PROVIDER: S-EPMC3499647 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature

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Modulation of bulbospinal rostral ventral lateral medulla neurons by hypoxia/hypercapnia but not medullary respiratory activity.

Boychuk Carie R CR Woerman Amanda L AL Mendelowitz David D

Hypertension (Dallas, Tex. : 1979) 20121029 6

Although sympathetic vasomotor discharge has respiratory modulation, the site(s) responsible for this cardiorespiratory interaction is unknown. One likely source for this coupling is the rostral ventral lateral medulla (RVLM), where presympathetic neurons originate in close apposition to respiratory neurons. The current study tested the hypothesis that RVLM bulbospinal neurons are modulated by medullary respiratory network activity using whole-cell patch-clamp electrophysiological recordings of ...[more]

PMID: 23108653

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Project description:Current understanding of the contribution of C1 neurons to blood pressure (BP) regulation derives predominantly from experiments performed in anesthetized animals or reduced ex vivo preparations. Here, we use ArchaerhodopsinT3.0 (ArchT) loss-of-function optogenetics to explore BP regulation by C1 neurons in intact, unanesthetized rats. Using a lentivirus that expresses ArchT under the Phox2b-activated promoter PRSx8 (PRSx8-ArchT), ?65% of transduced neurons were C1 (balance retrotrapezoid nucleus, RTN). Other rats received CaMKII-ArchT3.0 AAV2 (CaMKII-ArchT), which transduced C1 neurons and larger numbers of unidentified glutamatergic and GABAergic cells. Under anesthesia, ArchT photoactivation reduced sympathetic nerve activity and BP and silenced/strongly inhibited most (7/12) putative C1 neurons. In unanesthetized PRSx8-ArchT-treated rats breathing room air, bilateral ArchT photoactivation caused a very small BP reduction that was only slightly larger under hypercapnia (6% FiCO2), but was greatly enhanced during hypoxia (10 and 12% FiO2), after sino-aortic denervation, or during isoflurane anesthesia. The degree of hypotension correlated with percentage of ArchT-transduced C1 neurons. ArchT photoactivation produced similar BP changes in CaMKII-ArchT-treated rats. Photoactivation in PRSX8-ArchT rats reduced breathing frequency (FR), whereas FR increased in CaMKII-ArchT rats. We conclude that the BP drop elicited by ArchT activation resulted from C1 neuron inhibition and was unrelated to breathing changes. C1 neurons have low activity under normoxia, but their activation is important to BP stability during hypoxia or anesthesia and contributes greatly to the hypertension caused by baroreceptor deafferentation. Finally, C1 neurons are marginally activated by hypercapnia and the large breathing stimulation caused by this stimulus has very little impact on resting BP.SIGNIFICANCE STATEMENT C1 neurons are glutamatergic/peptidergic/catecholaminergic neurons located in the medulla oblongata, which may operate as a switchboard for differential, behavior-appropriate activation of selected sympathetic efferents. Based largely on experimentation in anesthetized or reduced preparations, a rostrally located subset of C1 neurons may contribute to both BP stabilization and dysregulation (hypertension). Here, we used Archaerhodopsin-based loss-of-function optogenetics to explore the contribution of these neurons to BP in conscious rats. The results suggest that C1 neurons contribute little to resting BP under normoxia or hypercapnia, C1 neuron discharge is restrained continuously by arterial baroreceptors, and C1 neuron activation is critical to stabilize BP under hypoxia or anesthesia. This optogenetic approach could also be useful to explore the role of C1 neurons during specific behaviors or in hypertensive models.

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Modulation of bulbospinal rostral ventral lateral medulla neurons by hypoxia/hypercapnia but not medullary respiratory activity.

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Modulation of bulbospinal rostral ventral lateral medulla neurons by hypoxia/hypercapnia but not medullary respiratory activity.

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