Multiple excitatory actions of orexins upon thalamo-cortical neurons in dorsal lateral geniculate nucleus - implications for vision modulation by arousal

Lukasz Chrobok,Marian Henryk Lewandowski,Katarzyna Palus-Chramiec,Anna Chrzanowska,Mariusz Kepczynski

doi:10.1038/s41598-017-08202-8

Lukasz Chrobok, Marian Henryk Lewandowski + Show 3 more

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https://doi.org/10.1038/s41598-017-08202-8

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Journal: Scientific Reports	Publication Date: Aug 9, 2017
Citations: 23	License type: open-access

Affiliation: Jagiellonian University

Abstract

The orexinergic system of the lateral hypothalamus plays a crucial role in maintaining wakefulness and mediating arousal in a circadian time-dependent manner. Due to the extensive connections of orexinergic neurons, both orexins (OXA and OXB) exert mainly excitatory effects upon remote brain areas, including the thalamus. The dorsal lateral geniculate nucleus (DLG) is a relay thalamic centre for the visual system. Its thalamo-cortical (TC) neurons convey photic information from the retina to the primary visual cortex. The present study shows that orexins are powerful modulators of neuronal activity in the DLG. OXA directly depolarised the majority of neurons tested, acting predominately on postsynaptic OX2 receptors. Moreover, OXA was found to increase excitability and enhance neuronal responses to both glutamate and γ-aminobutyric acid (GABA). Mechanistic studies showed the involvement of voltage-gated calcium currents and GIRK channels in the observed depolarisations. Immunohistochemical staining showed sparse orexinergic innervation of the DLG during the light phase, with increased density at night. We hypothesise that the depolarising effects of orexins upon DLG neurons may facilitate signal transmission through the visual thalamo-cortical pathway during behavioural arousal. Thus, the action of orexin on DLG TC neurons may underlie the circadian/behavioural modulation of vision.

Highlights

The orexins/hypocretins are two neuropeptides synthesised from a common precursor in a group of neurons localised in the lateral hypothalamus and perifornical area[1,2,3] that extensively innervate many nuclei in the brain[4]
Two distinct subpopulations of neurons can be found in the dorsal lateral geniculate nucleus (DLG): excitatory thalamo-cortical (TC) neurons that project an axon to the primary visual cortex and GABAergic interneurons, identified by their characteristic morphology and electrophysiology[44, 45] (Fig. 1A)
In our patch-clamp study, we focused on TC neurons to examine their possible sensitivity to orexins

Summary

Introduction

The orexins/hypocretins (orexin A/hypocretin 1 and orexin B/hypocretin 2) are two neuropeptides synthesised from a common precursor in a group of neurons localised in the lateral hypothalamus and perifornical area[1,2,3] that extensively innervate many nuclei in the brain[4]. Thalamo-cortical (TC) neurons are depolarised by neurotransmitters such as acetylcholine or noradrenaline, which promotes sensory transmission during arousal[25, 26, 27]. These classical neurotransmitters are known to modulate signal transmission from the thalamus to the cortex across the sleep-wake cycle[28, 29], and a similar role of the orexinergic system at the level of the thalamus has been suggested[12, 30]. The aim of this study was to determine if orexin A (OXA) and orexin B (OXB) have modulatory effects upon DLG TC neuronal activity. To the best of our knowledge, the present study shows for the first time the excitatory effects of orexins on the primary visual thalamus

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