Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2007 Jun 13;27(24):6412-6.
doi: 10.1523/JNEUROSCI.1432-07.2007.

Suprachiasmatic modulation of noradrenaline release in the ventrolateral preoptic nucleus

Benoît Saint-Mleux  1 , Laurence Bayer, Emmanuel Eggermann, Barbara E Jones, Michel Mühlethaler, Mauro Serafin
Affiliations

Suprachiasmatic modulation of noradrenaline release in the ventrolateral preoptic nucleus

Benoît Saint-Mleux et al. J Neurosci. .

Abstract

As the major brain circadian pacemaker, the suprachiasmatic nucleus (SCN) is known to influence the timing of sleep and waking. We thus investigated here the effect of SCN stimulation on neurons of the ventrolateral preoptic nucleus (VLPO) thought to be involved in promoting sleep. Using an acute in vitro preparation of the rat anterior hypothalamus/preoptic area, we found that whereas single-pulse stimulations of the SCN evoked standard fast ionotropic IPSPs and EPSPs, train stimulations unexpectedly evoked a long-lasting inhibition (LLI). Such LLIs could also be evoked in VLPO neurons by pressure application of NMDA within the SCN, indicating the specific activation of SCN neurons. This LLI was shown to result from the presynaptic facilitation of noradrenaline release, because it was suppressed in presence of yohimbine, a selective antagonist of alpha2-adrenoreceptors. The LLI depended on the opening of a potassium conductance, because it was annulled at E(K) and could be reversed below E(K). These results show that the SCN can provide an LLI of the sleep-promoting VLPO neurons that could play a role in the circadian organization of the sleep-waking cycle.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
Multiple effects of SCN stimulation on identified sleep-promoting VLPO neurons. A, Schematic view of the acute AH/POA horizontal slice preparation. Insets, Sections (lines a–c) performed to prepare the horizontal slice (left inset) and a typical triangular-shaped neuron recorded in the VLPO (right inset). B, C, A typical VLPO neuron recorded in whole-cell configuration in the current-clamp mode displays a low-threshold spike at the end of a hyperpolarizing current step (B) and is transiently hyperpolarized and inhibited (C) by bath-applied NA. D–F, In voltage-clamp mode, SCN single-pulse stimulations (*; 200 μA) evoke NBQX (25 μm)-sensitive EPSCs (D), bicuculline (20 μm)-sensitive IPSCs (E), or a mixture of both (F). Traces in D–F are an average of 10 consecutive stimulations. G, Whereas an SCN single-pulse stimulation (200 μA; G1, *) evokes a unique PSC (dot in inset), train stimulations of increasing duration (G2, **; G3, ***) evoke, in addition to reliable PSCs after each single stimulation (G2, dots in inset), a long-lasting outward current (G2, G3, arrowheads). As evident when recording the same neuron in current-clamp mode, such a current subtended a long-lasting hyperpolarization (G3, inset). 3V, Third ventricle; opt, optic tract; ox, optic chiasm; Bic, bicuculline.
Figure 2.
Figure 2.
LLI in the firing of identified VLPO neurons depends on SCN stimulation. A, Typical NA-induced inhibition of a VLPO neuron recorded in loose-attached cell configuration. B, Twenty hertz SCN train stimulations (B1, *) in contrast with 2 Hz train stimulations (B2, dots) produce an LLI. C, SCN train stimulations of increasing amplitude [C1, 30 μA (*); C2, 50 μA (**); C3, 70 μA (***)] produce an LLI of increasing duration and strength in an identified VLPO neuron. D, The SCN-evoked (*; 200 μA) LLI (D1) is totally (D2) and reversibly (D3) prevented in presence of a high-magnesium/low-calcium-containing ACSF known to interfere with synaptic transmission. E, Two regions (a and b) stimulated successively while recording from the same identified VLPO neurons are shown in a schematic view of a selected region of the AH/POA horizontal slice preparation. F, Train stimulation (*; 150 μA) applied in the SCN (region a) inhibits the firing of the neuron (Fa), whereas an even higher intensity of stimulation (**; 300 μA) applied outside of the SCN (region b) has no effect on its discharge (Fb). G, Train stimulations applied in the SCN (left) but not in the optic chiasm (right) produce an LLI. H, Electrical and chemical stimulations are applied successively in the SCN (region a) while recording the same identified VLPO neuron. I, The same VLPO neuron is inhibited by SCN train stimulation (I1) and by local pressure application of NMDA at 1 mm within the SCN (I2). 3V, Third ventricle; Cx, cortex; opt, optic tract; Ox, optic chiasm; ON, optic nerve; stim, stimulation
Figure 3.
Figure 3.
SCN-evoked LLI of identified VLPO neurons depends on the release of noradrenaline. A, C, In control conditions, both a train stimulation (A, *) and selective activation of SCN neurons by pressure ejection of NMDA at 1 mm within the SCN (C) evoke an LLI in identified VLPO neurons. B, D, In the presence of yohimbine at 2 μm, a selective antagonist of α2-adrenoreceptors, none of these inhibitory effects (compare A with B and C with D) can be evoked. E, F, In presence of NBQX, APV, and bicuculline (Bic), SCN train stimulation (*; 200 μA) evokes an LLHP in an identified VLPO neuron (E), which completely disappears in the presence of yohimbine at 2 μm (F). G, The LLHP observed at the resting membrane potential (G1) in response to SCN train stimulation (*; 200 μA) is annulled at EK (G2), the equilibrium potential for potassium, and is reversed below EK (G3).
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Abrahamson EE, Moore RY. Lesions of suprachiasmatic nucleus efferents selectively affect rest-activity rhythm. Mol Cell Endocrinol. 2006;252:46–56. - PubMed
    1. Chou TC, Bjorkum AA, Gaus SE, Lu J, Scammell TE, Saper CB. Afferents to the ventrolateral preoptic nucleus. J Neurosci. 2002;22:977–990. - PMC - PubMed
    1. Deboer T, Vansteensel MJ, Detari L, Meijer JH. Sleep states alter activity of suprachiasmatic nucleus neurons. Nat Neurosci. 2003;6:1086–1090. - PubMed
    1. Deurveilher S, Burns J, Semba K. Indirect projections from the suprachiasmatic nucleus to the ventrolateral preoptic nucleus: a dual tract-tracing study in rat. Eur J Neurosci. 2002;16:1195–1213. - PubMed
    1. Gallopin T, Fort P, Eggermann E, Cauli B, Luppi PH, Rossier J, Audinat E, Mühlethaler M, Serafin M. Identification of sleep-promoting neurons in vitro. Nature. 2000;404:992–995. - PubMed

Publication types

MeSH terms