Orexin-A Increases the Firing Activity of Hippocampal CA1 Neurons Through Orexin-1 Receptors

被引:50
作者
Chen, Xin-Yi [1 ]
Chen, Lei [2 ]
Du, Yi-Feng [1 ]
机构
[1] Shandong Univ, Prov Hosp, Dept Neurol, 324 Jingwu Rd, Jinan 250021, Shandong, Peoples R China
[2] Qingdao Univ, Dept Physiol, Qingdao, Peoples R China
基金
中国国家自然科学基金;
关键词
hippocampus; CA1; neurons; orexin-A; OX1; receptors; single-unit recording; LONG-TERM POTENTIATION; PYRAMIDAL NEURONS; DORSAL RAPHE; RAT-BRAIN; DIFFERENTIAL DISTRIBUTION; FUNCTIONAL INACTIVATION; SYNAPTIC PLASTICITY; SEROTONIN NEURONS; MESSENGER-RNA; IN-VIVO;
D O I
10.1002/jnr.23975
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Orexins including two peptides, orexin-A and orexin-B, are produced in the posterior lateral hypothalamus. Much evidence has indicated that central orexinergic systems play numerous functions including energy metabolism, feeding behavior, sleep/wakefulness, and neuroendocrine and sympathetic activation. Morphological studies have shown that the hippocampal CA1 regions receive orexinergic innervation originating from the hypothalamus. Positive orexin-1 (OX1) receptors are detected in the CA1 regions. Previous behavioral studies have shown that microinjection of OX1 receptor antagonist into the hippocampus impairs acquisition and consolidation of spatial memory. However, up to now, little has been known about the direct electrophysiological effects of orexin-A on hippocampal CA1 neurons. Employing multibarrel single-unit extracellular recordings, the present study showed that micropressure administration of orexin-A significantly increased the spontaneous firing rate from 2.96 +/- 0.85 to 8.45 +/- 1.86Hz (P<0.001) in 15 out of the 23 hippocampal CA1 neurons in male rats. Furthermore, application of the specific OX1 receptor antagonist SB-334867 alone significantly decreased the firing rate from 4.02 +/- 1.08 to 2.11 +/- 0.58Hz in 7 out of the 17 neurons (P<0.05), suggesting that endogenous orexinergic systems modulate the firing activity of CA1 neurons. Coapplication of SB-334867 completely blocked orexin-A-induced excitation of hippocampal CA1 neurons. The PLC pathway may be involved in activation of OX1 receptor-induced excitation of CA1 neurons. Taken together, the present study's results suggest that orexin-A produces excitatory effects on hippocampal neurons via OX1 receptors. (C) 2016 Wiley Periodicals, Inc.
引用
收藏
页码:1415 / 1426
页数:12
相关论文
共 84 条
[11]   Functional inactivation of orexin 1 receptors in the cerebellum disrupts trace eyeblink conditioning and local theta oscillations in guinea pigs [J].
Chen, Hao ;
Yang, Li ;
Chen, Fang ;
Yan, Jie ;
Yang, Nian ;
Wang, Yi-jie ;
Zhu, Zhi-ru ;
Hu, Zhi-an ;
Sui, Jian-feng ;
Hu, Bo .
BEHAVIOURAL BRAIN RESEARCH, 2013, 250 :114-122
[12]   Differential distribution of orexin-A and orexin-B immunoreactivity in the rat brain and spinal cord [J].
Cutler, DJ ;
Morris, R ;
Sheridhar, V ;
Wattam, TAK ;
Holmes, S ;
Patel, S ;
Arch, JRS ;
Wilson, S ;
Buckingham, RE ;
Evans, ML ;
Leslie, RA ;
Williams, G .
PEPTIDES, 1999, 20 (12) :1455-1470
[13]   Orexin receptors exert a neuroprotective effect in Alzheimer's disease (AD) via heterodimerization with GPR103 [J].
Davies, Julie ;
Chen, Jing ;
Pink, Ryan ;
Carter, David ;
Saunders, Nigel ;
Sotiriadis, Georgios ;
Bai, Bo ;
Pan, Yanyou ;
Howlett, David ;
Payne, Annette ;
Randeva, Harpal ;
Karteris, Emmanouil .
SCIENTIFIC REPORTS, 2015, 5
[14]   The hypocretins: Hypothalamus-specific peptides with neuroexcitatory activity [J].
De Lecea, L ;
Kilduff, TS ;
Peyron, C ;
Gao, XB ;
Foye, PE ;
Danielson, PE ;
Fukuhara, C ;
Battenberg, ELF ;
Gautvik, VT ;
Bartlett, FS ;
Frankel, WN ;
van den Pol, AN ;
Bloom, FE ;
Gautvik, KM ;
Sutcliffe, JG .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (01) :322-327
[15]   Cellular location and major terminal networks of the orexinergic system in the brain of two megachiropterans [J].
Dell, Leigh-Anne ;
Kruger, Jean-Leigh ;
Pettigrew, John D. ;
Manger, Paul R. .
JOURNAL OF CHEMICAL NEUROANATOMY, 2013, 53 :64-71
[16]   Pharmacological and molecular enhancement of learning in aging and Alzheimer's disease [J].
Disterhoft, JF ;
Oh, MM .
JOURNAL OF PHYSIOLOGY-PARIS, 2006, 99 (2-3) :180-192
[17]   Orexin (hypocretin)/dynorphin neurons control GABAergic inputs to tuberomammillary neurons [J].
Eriksson, KS ;
Sergeeva, OA ;
Selbach, O ;
Haas, HL .
EUROPEAN JOURNAL OF NEUROSCIENCE, 2004, 19 (05) :1278-1284
[18]   Fos expression in orexin neurons varies with behavioral state [J].
Estabrooke, IV ;
McCarthy, MT ;
Ko, E ;
Chou, TC ;
Chemelli, RM ;
Yanagisawa, M ;
Saper, CB ;
Scammell, TE .
JOURNAL OF NEUROSCIENCE, 2001, 21 (05) :1656-1662
[19]   Effect of orexin-A on discharge rate of rat suprachiasmatic nucleus neurons in vitro [J].
Farkas, B ;
Világi, I ;
Détári, L .
ACTA BIOLOGICA HUNGARICA, 2002, 53 (04) :435-443
[20]   Possible Role of Orexin in the Pathogenesis of Alzheimer Disease [J].
Ferini-Strambi, Luigi .
JAMA NEUROLOGY, 2014, 71 (12) :1478-1480