title: Orexin-A increases the firing activity of hippocampal CA1 neurons through orexin-1 receptors.
abstract: 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 OX1receptor 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 ± 1.86 Hz (P < 0.001) in 15 out of the 23 hippocampal CA1 neurons in male rats. Furthermore, application of the specific OX1receptor antagonist SB-334867 alone significantly decreased the firing rate from 4.02 ± 1.08 to 2.11 ± 0.58 Hz 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 OX1receptor-induced excitation of CA1 neurons. Taken together, the present study's results suggest that orexin-A produces excitatory effects on hippocampal neurons via OX1receptors. © 2016 Wiley Periodicals, Inc.
authors: Department of Neurology, Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China.
authors: Xin-Yi
authors: XY
authors: Chen
authors: Department of Physiology, Qingdao University, Qingdao, China.
authors: Lei
authors: L
authors: Chen
authors: Department of Neurology, Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China.
authors: Yi-Feng
authors: YF
authors: Du
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D064446:Orexin Receptors / Q000819:agonists / Q000502:physiology*; D000068797:Orexins / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: C497459:Hcrtr1 protein, mouse; D064446:Orexin Receptors; D000068797:Orexins
keywords: CA1 neurons; OX1 receptors; hippocampus; orexin-A; single-unit recording