Department of Neurophysiology and Chronobiology, Institute of Zoology and Biomedical Research, Jagiellonian University in Krakow, Gronostajowa 9 Street, 30-387, Krakow, Poland.
Faculty of Chemistry, Jagiellonian University in Krakow, Ingardena 3 Street, 30-060, Krakow, Poland.
Sci Rep. 2017 Aug 9;7(1):7713. doi: 10.1038/s41598-017-08202-8.
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 OX 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.
外侧下丘脑的食欲素能系统在维持觉醒和以昼夜节律依赖的方式调节觉醒方面起着至关重要的作用。由于食欲素神经元的广泛连接，两种食欲素（OXA 和 OXB）主要对包括丘脑在内的远程脑区产生兴奋作用。背外侧膝状体（DLG）是视觉系统的中继丘脑中心。其丘脑皮质（TC）神经元将光信息从视网膜传递到初级视觉皮层。本研究表明，食欲素是 DLG 神经元活动的强大调节剂。OXA 直接去极化了大多数测试的神经元，主要作用于突触后 OX 受体。此外，发现 OXA 可增加兴奋性并增强神经元对谷氨酸和γ-氨基丁酸（GABA）的反应。机制研究表明，观察到的去极化涉及电压门控钙电流和 GIRK 通道。免疫组织化学染色显示，在光照阶段，DLG 有稀疏的食欲素能传入，夜间密度增加。我们假设食欲素对 DLG 神经元的去极化作用可能有助于在行为觉醒期间通过视觉丘脑皮质通路进行信号传递。因此，食欲素对 DLG TC 神经元的作用可能是昼夜节律/行为调节视觉的基础。
