title: Orexin-A excites pyramidal neurons in layer 2/3 of the rat prefrontal cortex.
abstract: The arousal peptides, orexins, play an important role in regulating the function of the prefrontal cortex (PFC). Although orexins have been shown to increase the excitability of deep-layer neurons in the medial prefrontal cortex (mPFC), little is known about their effect on layer 2/3, the main intracortical processing layer. In this study, we investigated the effect of orexin-A on pyramidal neurons in layer 2/3 of the mPFC using whole-cell recordings in rat brain slices. We observed that orexin-A reversibly depolarized layer 2/3 pyramidal neurons through a postsynaptic action. This depolarization was concentration-dependent and mediated via orexin receptor 1. In voltage-clamp recordings, the orexin-A-induced current was reduced by the replacement of internal K(+) with Cs(+), removal of external Na(+), or an application of flufenamic acid (an inhibitor of nonselective cation channels). A blocker of Na(+)/Ca(2+) exchangers (SN-6) did not influence the excitatory effect of orexin-A. Moreover, the current induced by orexin-A reversed near E(k) when the external solution contained low levels of Na(+). When recording with Cs(+)-containing pipettes in normal external solution, the reversal potential of the current was approximately -25 mV. These data suggest an involvement of both K(+) channels and nonselective cation channels in the effect of orexin-A. The direct excitatory action of orexin-A on layer 2/3 mPFC neurons may contribute to the modulation of PFC activity, and play a role in cognitive arousal.
authors.affiliation: Department of Physiology, Third Military Medical University, Chongqing, PR China.
authors.forename: Jie
authors.initials: J
authors.lastname: Yan
authors.forename: Chao
authors.initials: C
authors.lastname: He
authors.forename: Jian-Xia
authors.initials: JX
authors.lastname: Xia
authors.forename: Dan
authors.initials: D
authors.lastname: Zhang
authors.forename: Zhi-An
authors.initials: ZA
authors.lastname: Hu
mesh_terms: D000818:Animals; D066298:In Vitro Techniques; D047908:Intracellular Signaling Peptides and Proteins / Q000494:pharmacology / Q000502:physiology*; D007473:Ion Channels / Q000502:physiology*; D009479:Neuropeptides / Q000494:pharmacology / Q000502:physiology*; D064446:Orexin Receptors; D000068797:Orexins; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000502:physiology; D017397:Prefrontal Cortex / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D043562:Receptors, G-Protein-Coupled / Q000502:physiology; D018013:Receptors, Neuropeptide / Q000502:physiology; D019831:Sodium-Calcium Exchanger / Q000502:physiology
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D007473:Ion Channels; D009479:Neuropeptides; D064446:Orexin Receptors; D000068797:Orexins; D015221:Potassium Channels; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide; D019831:Sodium-Calcium Exchanger