Cardiovascular Responses to Chemical Stimulation of the Hypothalamic Arcuate Nucleus in the Rat: Role of the Hypothalamic Paraventricular Nucleus

Kawabe, Takao; Kawabe, Kazumi; Sapru, Hreday N.

doi:10.1371/journal.pone.0045180

Cited by 37 publications

(70 citation statements)

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“…In this and other series of experiments, the ARCN was always identified by microinjections of NMDA (10 mM), which elicited decreases in MAP (19 Ϯ 1 mmHg) and increases in HR (46 Ϯ 3 beats/min, n ϭ 9) in nonbarodenervated rats (26). Time intervals between the microinjection and beginning of the response (onset) and maximum response (peak) and the end of the response (duration) were noted.…”

Section: Resultssupporting

confidence: 53%

“…We have recently shown that microinjections of N-methyl-D-aspartic acid (NMDA) into the ARCN elicited an increase in heart rate (HR) in rats regardless of whether the baroreceptors were intact or denervated (26,27,36). Tachycardic responses elicited from the ARCN are mediated via the release of glutamate and ␣-melanocyte-stimulating hormone (␣-MSH) in the hypothalamic paraventricular nucleus (PVN) because blockade of ionotropic glutamate receptors (iGLURs) and melanocortin 3/4 receptors in the ipsilateral PVN attenuated these responses (27).…”

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confidence: 99%

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GABA and glycine receptors in the nucleus ambiguus mediate tachycardia elicited by chemical stimulation of the hypothalamic arcuate nucleus

Chitravanshi

Kawabe

Sapru

2015

American Journal of Physiology-Heart and Circulatory Physiology

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elicits tachycardia, which is partially mediated via inhibition of vagal inputs to the heart. The neuronal pools and neurotransmitters in them mediating tachycardia elicited from the ARCN have not been identified. We tested the hypothesis that the tachycardia elicited from the ARCN may be mediated by inhibitory neurotransmitters in the nucleus ambiguus (nAmb). Experiments were done in urethane-anesthetized, artificially ventilated, male Wistar rats. In separate groups of rats, unilateral and bilateral microinjections of muscimol (1 mM), gabazine (0.01 mM), and strychnine (0.5 mM) into the nAmb significantly attenuated tachycardia elicited by unilateral microinjections of NMDA (10 mM) into the ARCN. Histological examination of the brains showed that the microinjections sites were within the targeted nuclei. Retrograde anatomic tracing from the nAmb revealed direct bilateral projections from the ARCN and hypothalamic paraventricular nucleus to the nAmb. The results of the present study suggest that tachycardia elicited by stimulation of the ARCN by microinjections of NMDA is mediated via GABAA and glycine receptors located in the nAmb.

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Section: Resultssupporting

confidence: 53%

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confidence: 99%

GABA and glycine receptors in the nucleus ambiguus mediate tachycardia elicited by chemical stimulation of the hypothalamic arcuate nucleus

Chitravanshi

Kawabe

Sapru

2015

American Journal of Physiology-Heart and Circulatory Physiology

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“…In the mouse DMH, we observed a significant number of RVLM-projecting neurons; however, the number was far smaller than when the CtB injections encompassed the raphe pallidus significant decreases in SNA, MAP, and HR, because NPY inhibits a G protein-activated inwardly rectifying K (GIRK) current (39-41), which can hyperpolarize to a greater extent than GABA A receptors, which open Cl channels. While the limited inhibition by GABA was expected, the effect of PVN AgRP on SNA in rats is controversial (8,42). Here, we show that doses of PVN AgRP that exceed those required to elicit food intake and sufficient to decrease body temperature failed to decrease SSNA, AP, or HR.…”

Section: Discussionmentioning

confidence: 69%

“…Based on anatomical evidence that PVN presympathetic neurons are richly innervated by ArcN NPY fibers in mice ( Figure 2) and rats (4), the strong sympathoinhibitory effects of NPY in the PVN in mice (Figure 3) and rats (4), and indirect evidence in rats that ArcN NPY neurons inhibit SNA via a synapse in the PVN (5,7,8), we were surprised that blockade of PVN NPY1R only weakly reversed the effects of select ArcN NPY/AgRP neuronal activation. In sharp contrast, blockade of DMH NPY1R completely reversed these effects.…”

Section: Discussionmentioning

confidence: 99%

“…Indirect evidence implicates an NPY projection from the ArcN. More specifically, injections of leptin or insulin into the ArcN, or nonspecific activation of the ArcN, increase SNA in part via suppression of tonic NPY inhibition of PVN presympathetic neurons (5,7,8). However, whether the PVN NPY input that is suppressed by insulin and leptin originates directly from neurons in the ArcN has not been established.…”

Section: Introductionmentioning

confidence: 99%

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Arcuate neuropeptide Y inhibits sympathetic nerve activity via multiple neuropathways

Shi¹,

Madden²,

Brooks³

2017

Journal of Clinical Investigation

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Obesity increases sympathetic nerve activity (SNA) via activation of proopiomelanocortin neurons in the arcuate nucleus (ArcN), and this action requires simultaneous withdrawal of tonic neuropeptide Y (NPY) sympathoinhibition. However, the sites and neurocircuitry by which NPY decreases SNA are unclear. Here, using designer receptors exclusively activated by designer drugs (DREADDs) to selectively activate or inhibit ArcN NPY neurons expressing agouti-related peptide (AgRP) in mice, we have demonstrated that this neuronal population tonically suppresses splanchnic SNA (SSNA), arterial pressure, and heart rate via projections to the paraventricular nucleus (PVN) and dorsomedial hypothalamus (DMH The Journal of Clinical Investigation R E S E A R C H A R T I C L E2 8 6 9 jci.org Volume 127 Number 7 July 2017We next tested whether selective excitation or inhibition of ArcN NPY/AgRP neurons alters splanchnic SNA (SSNA), mean AP (MAP), or heart rate (HR) ( Figure 1). As shown in representative experiments ( Figure 1, A and B) and grouped data ( Figure 1C), in ArcN hM3Dq mice, i.p. CNO (0.3 mg/kg) promptly decreased SSNA, MAP, and HR, whereas i.p. saline had no effects. The suppression induced by CNO was sustained for at least 1 hour, and, in mice with longer recordings, up to 4 hours (data not shown). In rats, guinea pigs, and humans, CNO can have nonspecific effects due to its conversion to clozapine (17, 18). However, in WT mice receiving the Cre-dependent hM3Dq vector, neither i.p. saline nor CNO significantly altered these variables, suggesting that CNO was not exerting its effects independently of DREADD activation. A separate group of Agrp-IRES-Cre mice instead received AAV-hM4Di-mCherry in the ArcN (Figure 1, D-F). In these ArcN hM4Di mice, i.p. CNO (0.3 and 1 mg/kg) dose-dependently increased SSNA, MAP, and HR, although the responses developed both NPY-GFP and Cre in AgRP neurons. In agreement with an earlier study using a different approach (14), we found that while not all NPY-GFP neurons had visible hM3Dq-mCherry labeling, 100% of the hM3Dq-mCherry-marked neurons also expressed NPY-GFP (Supplemental Figure 1; supplemental material available online with this article; https://doi.org/10.1172/JCI92008DS1). WT mice never expressed the Cre-dependent DREADD. In a second set of experiments, 2 or more weeks after Agrp-IRES-Cre mice received hM3Dq bilaterally in the ArcN, CNO (0.3 mg/kg) or the saline vehicle was administered i.p., and food intake was monitored for the following 4 hours. As shown previously (14), i.p. CNO, but not saline, rapidly evoked food intake in ArcN hM3Dq mice (Supplemental Figure 1). Conversely, activation of inhibitory DREADDs in ArcN hM4Di mice at the beginning of the feeding period (lights out) inhibited food intake (Supplemental Figure 1). Therefore, we anatomically and functionally confirm that this approach selectively targets ArcN NPY/AgRP neurons. The Journal of Clinical Investigation R E S E A R C H A R T I C L E2 8 7 0jci.org Volume 127 Number 7 July 2017neurons were also observ...

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Fos‐CreER‐based genetic mapping of forebrain regions activated by acupuncture

Guo

Lin

Samaniego

et al. 2019

J of Comparative Neurology

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Acupuncture increasingly is accepted as a potential therapy for many diseases in the Western world. However, the mechanism of acupuncture is not well understood mechanistically. We have established that manual acupuncture (MA) at the Neiguan (P6) acupoint inhibits excitatory cardiovascular reflex responses through modulation of the autonomic nervous system in the brainstem. It is unclear whether P6 MA activates neurons in the brain regions beyond the brainstem. Thus, we mapped P6 specific neural activation by MA in the forebrain using the Fos-CreER; Ai9 mice model, which allows for enhanced sensitivity and efficiency compared to conventional immunohistochemical staining. Compared to sham-MA control without manual stimulation, we find that MA at P6 markedly increases c-Fos positive neurons in a number of the forebrain regions (n = 5 in each group). These activated regions include accumbens nucleus, caudate putamen, claustrum, bed nucleus of the stria terminalis, amygdaloid nucleus, ventral posterior division of the thalamic nucleus, paraventricular hypothalamic nucleus, arcuate hypothalamic nucleus, primary and secondary somatosensory cortex, ectorhinal cortex, and dorsolateral entorhinal cortex. As MA at P6 activates neurons in relatively broad brain networks beyond the brainstem, our data suggest that acupuncture at this acupoint has the potential to influence physiological functions associated with autonomic and non-autonomic nervous systems through its effects on multiple brain regions.

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Cardiovascular Responses to Chemical Stimulation of the Hypothalamic Arcuate Nucleus in the Rat: Role of the Hypothalamic Paraventricular Nucleus

Cited by 37 publications

References 56 publications

GABA and glycine receptors in the nucleus ambiguus mediate tachycardia elicited by chemical stimulation of the hypothalamic arcuate nucleus

GABA and glycine receptors in the nucleus ambiguus mediate tachycardia elicited by chemical stimulation of the hypothalamic arcuate nucleus

Arcuate neuropeptide Y inhibits sympathetic nerve activity via multiple neuropathways

Fos‐CreER‐based genetic mapping of forebrain regions activated by acupuncture

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