Noradrenergic regulation of parvocellular neurons in the rat hypothalamic paraventricular nucleus

doi:10.1016/S0306-4522(00)00003-8

Neuroscience

Volume 96, Issue 4, March 2000, Pages 743-751

https://doi.org/10.1016/S0306-4522(00)00003-8 Get rights and content

Abstract

Noradrenergic projections to the hypothalamic paraventricular nucleus have been implicated in the secretory regulation of several anterior pituitary hormones, including adrenocorticotropin, thyroid-stimulating hormone, growth hormone and prolactin. In an attempt to elucidate the effects of norepinephrine on the central control of pituitary hormone secretion, we looked at the actions of norepinephrine on the electrical properties of putative parvocellular neurons of the paraventricular nucleus using whole-cell current-clamp recordings in hypothalamic slices. About half (51%) of the putative parvocellular neurons recorded responded to norepinephrine with either a synaptic excitation or a direct inhibition. Norepinephrine (30–300 μM) caused a marked increase in the frequency of excitatory postsynaptic potentials in about 36% of the parvocellular neurons recorded. The increase in excitatory postsynaptic potentials was blocked by prazosin (10 μM), but not by propranolol (10 μM) or timolol (20 μM), indicating that it was mediated by α₁-adrenoreceptor activation. It was also blocked by ionotropic glutamate receptor antagonists, suggesting that the excitatory postsynaptic potentials were caused by glutamate release. The increase in excitatory postsynaptic potentials was completely abolished by tetrodotoxin, indicating the spike dependence of the norepinephrine-induced glutamate release. In a separate group comprising 14% of the parvocellular neurons recorded, norepinephrine elicited a hyperpolarization (6.2±0.69 mV) that was blocked by the β-adrenoreceptor antagonists, propranolol (10 μM) and timolol (20 μM), but not by the α₁-receptor antagonist, prazosin (10 μM). This response was not blocked by tetrodotoxin (1.5–3 μM), suggesting that it was caused by a direct postsynaptic action of norepinephrine. The topographic distribution within the paraventricular nucleus of the norepinephrine-responsive and non-responsive parvocellular neurons was mapped based on intracellular biocytin labeling and neurophysin immunohistochemistry.

These data indicate that one parvocellular subpopulation, consisting of about 36% of the paraventricular parvocellular neurons, receives an excitatory input from norepinephrine-sensitive local glutamatergic interneurons, while a second, separate subpopulation, representing about 14% of the parvocellular neurons in the paraventricular nucleus, responds directly to norepinephrine with a β-adrenoreceptor-mediated inhibition. This suggests that excitatory inputs to parvocellular neurons of the paraventricular nucleus are mediated mainly by an intrahypothalamic glutamatergic relay, and that only a relatively small subset of paraventricular parvocellular neurons receives direct noradrenergic inputs, which are primarily inhibitory.

Section snippets

Slice preparation

Male Sprague–Dawley rats (75–150 g, Charles River, Wilmington, MA, U.S.A.) were deeply anesthetized with pentobarbitol sodium (50 mg/kg, body weight) and decapitated according to a protocol approved by the Tulane University Animal Care and Use Committee (PHS A3552-01). Every effort was made to minimize animal suffering and to reduce the number of animals used in this study. After decapitation, the brain was quickly and gently removed from the cranial cavity and immersed in cooled (1–2°C),

Results

Putative parvocellular neurons of the PVN were distinguished with a high degree of reliability from putative magnocellular neurons on the basis of specific electrophysiological properties.16., 45. In general, under current-clamp conditions, parvocellular neurons lack the transient outward rectification seen in magnocellular neurons and often show evidence of a low-threshold Ca²⁺ potential. A total of 111 putative parvocellular neurons were tested for their response to norepinephrine in this

Discussion

Little is known about the central effects of norepinephrine on hypothalamic parvocellular neuronal activity and hypophysiotropic hormone release. The present study characterizes for the first time the electrophysiological actions of norepinephrine in cells identified as parvocellular neurons of the PVN. Electrophysiological properties provide a reliable means of distinguishing between parvocellular and magnocellular neurons of the PVN,16., 45. and allow for the study of cell type-specific

Acknowledgements

This work was funded by National Institute of Neurological Disorders and Stroke Grant R29 NS31187. SSD was partially supported by a predoctoral fellowship from the Louisiana American Heart Association.

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Noradrenergic regulation of parvocellular neurons in the rat hypothalamic paraventricular nucleus

Abstract

Section snippets

Slice preparation

Results

Discussion

Acknowledgements

Bailliéres clin. endocrinol. Metab.

Brain Res.

Brain Res.

Life Sci.

Neuroscience

Brain Res.

Life Sci.

Brain Res. Bull.

Brain Res. Bull.

Brain Res. Bull.

Psychoneuroendocrinology

Interaction of beta-adrenergic agonists and antagonists with the stimulation of growth hormone release induced by clonidine or by morphine in the rat

J. Endocrinol.

Physiological evidence for local excitatory synaptic circuits in the rat hypothalamus

J. Neurophysiol.

Catecholamine effects upon rat hypothalamic corticotropin-releasing hormone secretion in vitro

J. clin. Invest.

Estrogen modulation of the alpha-1-adrenergic response of hypothalamic neurons

Neuroendocrinology

Relationship of alpha-1- and alpha-2-adrenergic-binding sites to regions of the paraventricular nucleus of the hypothalamus containing corticotropin-releasing factor and vasopressin neurons

Neuroendocrinology

Anatomical specificity of noradrenergic inputs to the paraventricular and supraoptic nuclei of the rat hypothalamus

J. comp. Neurol.

Effects of norepinephrine on the electrical properties of identified neurons of the hypothalamic paraventricular nucleus

Soc. Neurosci. Abstr.

Noradrenergic excitation of magnocellular neurons in the rat hypothalamic paraventricular nucleus via intranuclear glutamatergic circuits

J. Neurosci.

Noradrenergic afferents facilitate the activity of tuberoinfundibular neurons of the hypothalamic paraventricular nucleus

Neuroendocrinology

In vivo intracellular recording of neurones in and near the supraoptic nucleus of the rat hypothalamus: electrical and synaptic properties

J. Neuroendocrinol.

Effects of neurotransmitters on the release of corticotropin releasing hormone (CRH) by rat hypothalamic tissue in vitro

Expl Brain Res.

Thyrotropin releasing hormone (TRH): neurotransmitter regulation of secretion by mouse hypothalamic tissue in vitro

Endocrinology