Electrophysiological actions of orexins on rat suprachiasmatic neurons in vitro

doi:10.1016/j.neulet.2008.10.058

Neuroscience Letters

Volume 448, Issue 3, 31 December 2008, Pages 273-278

https://doi.org/10.1016/j.neulet.2008.10.058 Get rights and content

Abstract

The study of neural arousal mechanisms has been greatly aided by the discovery of the orexin peptides (orexin A and orexin B), the subsequent identification of the neurons that synthesize these peptides, their projections in the brain, and the distribution of orexin receptors in the central nervous system. Orexin neuron activation is partly controlled by circadian signals generated in the brain's main circadian pacemaker, the suprachiasmatic nuclei (SCN). The SCN clock is in turn reset by arousal-promoting stimuli and, intriguingly, orexin fibers and receptor expression are detected in the SCN region. It is unclear, however, if orexin can alter SCN neuronal activity. Here using a coronal brain slice preparation, we found that orexin A and orexin B (0.1–1 μM) elicited significant changes in the extracellularly recorded firing rate and firing pattern in ∼80% of rat SCN cells tested; the most common response was suppression of firing rate. Co-application of orexin A with a cocktail of ionotropic GABA and glutamate receptor antagonists did not alter the actions of this peptide on firing rate, but did change some its effects on firing pattern. We conclude that orexins can alter SCN neurophysiology and may influence the transmission of information through the SCN to other CNS regions.

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Acknowledgements

This work was funded by project grants from the BBSRC to HDP. We thank Elizabeth Greene and Dr. Helen Reed for technical assistance.

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Finally, we propose a coupling of orexinergic and retinal information on the same OPN neurons, which respond to both OXA and PAC1 receptor agonist. The modulation of neuronal activity in the subcortical visual system by orexins has been proposed before, for such areas as the lateral geniculate nucleus (LGN; all three parts) (Chrobok et al., 2021b; Chrobok et al., 2017; Chrobok et al., 2016; Orlowska-Feuer et al., 2019; Palus et al., 2015; Pekala et al., 2011), the SCN (Belle et al., 2014; Belle et al., 2017; Brown et al., 2008), or recently for the superior colliculus (Chrobok et al., 2021a). The functional connection between these two systems has also been strengthened by reports on orexin action in the retina (Qiao et al., 2017; Zhang et al., 2018) and the primary visual cortex (Bayer, 2004).
Pronounced environmental changes between the day and night led to evolution of specialised mechanisms organising their daily physiology, named circadian clocks. Currently, it has become clear that the master clock in the suprachiasmatic nuclei of the hypothalamus is not an exclusive brain site to generate daily rhythms. Indeed, several brain areas, including the subcortical visual system have been recently shown to change their neuronal activity across the daily cycle. Here we focus our investigation on the olivary pretectal nucleus (OPN) – a retinorecipient structure primarily involved in the pupillary light reflex. Using the multi-electrode array technology ex vivo we provide evidence for OPN neurons to elevate their firing during the behaviourally quiescent light phase. Additionally, we report the robust responsivity to orexin A via the identified OX₂ receptor in this pretectal centre, with higher responsiveness noted during the night. Interestingly, we likewise report a daily variation in the response to PAC1 receptor activation, with implications for the convergence of orexinergic and visual input on the same OPN neurons. Altogether, our report is first to suggest a daily modulation of the OPN activity via intrinsic and extrinsic mechanisms, organising its temporal physiology.
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Cholinergic cells have not been identified in the basal forebrain of Polypterus and, since they are not present in agnathans and exist in all other actiniopterygian and sarcopterygian vertebrates, this type of interaction would have appeared later in evolution [80]. The presence of a high OX-ir innervation in the suprachiasmatic nucleus is a general feature observed in all vertebrates [30,37,61,78,79,87,90,127], and this innervation can alter suprachiasmatic neuronal activity and influence the transmission of information to other brain regions [15,67]. Only few OX-ir fibers reach the median eminence of cladistians, suggesting a possible function in neuroendocrine regulation.
Cladistians are primitive actinopterygian fishes mostly neglected in neuroanatomical studies. In the present study, the detailed neuroanatomical distribution of orexin (hypocretin)-like immunoreactive (OX-ir) cell bodies and fibers was analyzed in the brain of two species representative of the two extant genera of cladistians. Antibodies against mammalian orexin-A and orexin-B peptides were used. Simultaneous detection of orexins with neuropeptide Y (NPY), tyrosine hydroxylase (TH), and serotonin (5-HT) was used to establish accurately the topography of the orexin system and to evaluate the possible interactions with NPY and monoaminergic systems. A largely common pattern of OX-ir distribution in the two cladistian species was observed. Most OX-ir cells were located in the suprachiasmatic nucleus and tuberal hypothalamus, whereas scarce cells were observed in the posterior tubercle. In addition, a population of OX-ir cells was found in the preoptic area only in Polypterus and some cells also contained TH. The observed widespread distribution of OX-ir fibers was especially abundant in the retrobulbar area, subpallial areas, preoptic area, suprachiasmatic nucleus, tuberal hypothalamic area, prethalamus, thalamus, pretectum, optic tectum, and tegmentum. Low innervation was found in relation to monoaminergic cell groups, whereas a high NPY innervation was observed in all OX-ir cell groups. These relationships would represent the anatomical substrate for the functional interdependence between these systems. The organization of the orexin system in cladistians revealed a pattern largely consistent with those reported for all studied groups of vertebrates, suggesting that the primitive organization of this peptidergic system occurred in the common ancestor of gnathostome vertebrates.

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¹: These authors contributed equally to this study.

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Electrophysiological actions of orexins on rat suprachiasmatic neurons in vitro

Abstract

Section snippets

Acknowledgements

J. Neurosci. Methods

Neuroscience

Prog. Neurobiol.

Neuroscience

Peptides

Neuroscience

Neuroscience

Neuroscience

Neuroscience

Brain Res.

J. Chem. Neuroanat.

Brain Res.

Orexin receptor1 (OX-R1) immunoreactivity in chemically defined neurons of the hypothalamus: focus on orexin targets involved in control of food and water intake

Eur. J. Neurosci.

Rhythmic changes in spike coding in the suprachiasmatic nucleus

J. Physiol.