Elsevier

Neuroscience

Volume 153, Issue 3, 15 May 2008, Pages 605-617
Neuroscience

Behavioural neuroscience
Cardiovascular function of a glutamatergic projection from the hypothalamic paraventricular nucleus to the nucleus tractus solitarius in the rat

https://doi.org/10.1016/j.neuroscience.2008.02.076Get rights and content

Abstract

Experiments were done in urethane-anesthetized, barodenervated, male Wistar rats. Chemical stimulation of the hypothalamic paraventricular nucleus (PVN) by unilateral microinjections of N-methyl-d-aspartic acid (NMDA) elicited increases in mean arterial pressure (MAP) and greater splanchnic nerve activity (GSNA). The increases in the MAP and GSNA induced by chemical stimulation of the PVN were significantly exaggerated by bilateral microinjections of d(−)-2-amino-7-phosphono-heptanoic acid (d-AP7) and 2,3-dioxo-6-nitro-1,2,3,4-tetrahydro-benzo[f]quinoxaline-7-sulfonamide disodium (NBQX) (ionotropic glutamate receptor antagonists) into the medial subnucleus of the nucleus tractus solitarius (mNTS). These results were confirmed by single unit recordings; i.e. excitation of mNTS barosensitive neurons caused by chemical stimulation of the ipsilateral PVN was blocked by application of d-AP7 and NBQX to these neurons. Bilateral microinjections of d-AP7 and NBQX into the mNTS elicited pressor responses which were significantly attenuated by inhibition of PVN neurons by bilateral microinjections of muscimol. Unilateral microinjections of fluorogold into the mNTS resulted in bilateral retrograde labeling of the PVN neurons. Unilateral microinjections of biotinylated dextran amine into the PVN resulted in anterograde labeling of axons and terminals in the mNTS bilaterally and the labeled terminals exhibited vesicular glutamate transporter-2 immunoreactivity. These results indicated that 1) a tonically active glutamatergic bilateral projection from the PVN to the mNTS exists; 2) bilateral blockade of ionotropic glutamate receptors in the mNTS exaggerates the increases in MAP and GSNA, but not heart rate, to the chemical stimulation of the PVN; and 3) this projection may serve as a restraint mechanism for excitatory cardiovascular effects of PVN stimulation.

Section snippets

General procedures

Experiments were done in adult male Wistar rats (Charles River Laboratories, Wilmington, MA, USA) weighing 300–380 g (n=73). All animals were housed under controlled conditions with a 12-h light/dark cycle. Food and water were available to the animals ad libitum. The experiments were performed according to the NIH guide for “The Care and Use of Laboratory Animals, 7th Edition, 1996” and with the approval of the Institutional Animal Care and Use Committee of this university. Every effort was

Concentration-response of NMDA in the PVN

Unilateral microinjections of NMDA into the PVN elicited increases in MAP and HR (Table 1A). Maximal pressor and tachycardic responses were elicited by 10 mM concentration; therefore, this concentration of NMDA was selected for further studies in other groups of rats. The onset, peak and duration of the responses elicited by 10 mM concentration of NMDA were 5–20 s, 1–2 min, and 10–15 min, respectively. In this and other series of experiments, microinjections of aCSF alone into the PVN and mNTS

Discussion

The following new observations were made in this study: 1) a glutamatergic bilateral projection from the PVN to the mNTS was identified, 2) bilateral blockade of ionotropic glutamate receptors in the mNTS exaggerated the pressor and sympathetic nerve, but not HR, responses to unilateral chemical stimulation of the PVN, and 3) the projection from the PVN to the mNTS was determined to be tonically active.

NMDA has been used to stimulate PVN in only a few investigations (Li et al 2001, Li et al 2006

Conclusion

In summary, using anatomical, physiological and electrophysiological techniques, we have demonstrated the presence of a glutamatergic projection from the PVN to the mNTS. The projection is bilateral with ipsilateral preponderance. Since the blockade of this projection in the mNTS exaggerated the pressor responses to the PVN stimulation, it may be concluded that its normal function is to restrain the excitatory cardiovascular effects of PVN stimulation. The projection from the PVN to the mNTS is

Acknowledgments

This work was supported in part by NIH grants HL024347 and HL076248 awarded to Dr. H. N. Sapru.

References (48)

  • R.C. Rogers et al.

    Gastric-vagal solitary neurons excited by paraventricular nucleus microstimulation

    J Auton Nerv Syst

    (1985)
  • H.N. Sapru et al.

    Aortic nerve stimulation in the rat: cardiovascular and respiratory responses

    Brain Res Bull

    (1981)
  • E. Shen et al.

    Hypovolemia induces Fos-like immunoreactivity in neurons of the rat supraoptic and paraventricular nuclei

    J Auton Nerv Syst

    (1992)
  • M.V. Sofroniew et al.

    Evidence for direct projection from oxytocin and vasopressin neurons in the hypothalamic paraventricular nucleus to the medulla oblongata: immunohistochemical visualization of both the horseradish peroxidase transported and the peptide produced by the same neurons

    Neurosci Lett

    (1981)
  • J.E. Stern

    Nitric oxide and homeostatic control: an intercellular signalling molecule contributing to autonomic and neuroendocrine integration?

    Prog Biophys Mol Biol

    (2004)
  • E. Viard et al.

    Cardiovascular responses to activation of metabotropic glutamate receptors in the nTS of the rat

    Brain Res

    (2002)
  • H. Yamashita et al.

    Decrease in blood pressure by stimulation of the rat hypothalamic paraventricular nucleus with L-glutamate or weak current

    J Auton Nerv Syst

    (1987)
  • D. Accorsi-Mendonca et al.

    Urethane inhibits the GABAergic neurotransmission in the nucleus of the solitary tract of rat brain stem slices

    Am J Physiol Regul Integr Comp Physiol

    (2007)
  • E. Badoer

    Hypothalamic paraventricular nucleus and cardiovascular regulation

    Clin Exp Pharmacol Physiol

    (2001)
  • T.W. Bailey et al.

    Vasopressin inhibits glutamate release via two distinct modes in the brainstem

    J Neurosci

    (2006)
  • D. Banks et al.

    Activation within dorsal medullary nuclei following stimulation in the hypothalamic paraventricular nucleus in rats

    Pflugers Arch

    (1987)
  • D.C. Braga et al.

    Central oxytocin modulates exercise-induced tachycardia

    Am J Physiol Regul Integr Comp Physiol

    (2000)
  • R.M. Buijs

    Intra- and extrahypothalamic vasopressin and oxytocin pathways in the ratPathways to the limbic system, medulla oblongata and spinal cord

    Cell Tissue Res

    (1978)
  • J.H. Coote

    The hypothalamus and cardiovascular regulation

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