Orexin Neurons Are Directly and Indirectly Regulated by Catecholamines in a Complex Manner

Abstract

Orexin neurons are directly and indirectly regulated by catecholamines in a complex manner. J Neurophysiol 96: 284 -298, 2006. First published April 12, 2006 doi:10.1152/jn.01361.2005. We reported elsewhere that orexin neurons are directly hyperpolarized by noradrenaline (NA) and dopamine. In the present study, we show that NA, dopamine, and adrenaline all directly hyperpolarized orexin neurons. This response was inhibited by the ␣ 2 adrenergic receptor (␣ 2 -AR) antagonist, idazoxan or BRL44408, and was mimicked by the ␣ 2 -AR-selective agonist, UK14304. A low concentration of Ba 2ϩ inhibited NA-induced hyperpolarization, which suggests that activation of G protein coupled inward rectifier potassium channels is involved in the response. In the presence of a high concentration of idazoxan, NA induced depolarization or inward current. This response was inhibited by ␣ 1 -AR antagonist, prazosin, which suggests the existence of ␣ 1 -ARs on the orexin neurons along with ␣ 2 -AR. We also examined the effects of NA on glutamatergic and GABAergic synaptic transmission. NA application dramatically increased the frequency and amplitude of spontaneous inhibitory synaptic currents (sIPSCs) and inhibited excitatory synaptic currents (sEPSCs) in orexin neurons; however, NA decreased the frequency of miniature EPSCs (mEPSCs) and IPSCs and the amplitude of evoked EPSCs and IPSCs through the ␣ 2 -AR, because the NA response on mPSCs was inhibited by idazoxan. These results suggest that the NA-induced increase in sIPSC frequency and amplitude is mediated via ␣ 1 -ARs on the somata of GABAergic neurons that innervate the orexin neurons. Calcium imaging using orexin/YC2.1 transgenic mouse brain revealed that NA-induced inhibition of orexin neurons is not altered by sleep deprivation or circadian time in mice. The evidence presented here revealed that orexin neurons are regulated by catecholamines in a complex manner.

Selective loss of GABA B receptors in orexin-producing neurons results in disrupted sleep/wakefulness architecture

“…We have previously studied the regulatory mechanisms of orexin neurons in vitro (7,8,19,(23)(24)(25). However, the physiological relevance of the regulatory mechanisms or inputs affecting the activity of orexin neurons remains unknown.…”

Vasopressin Increases Locomotion through a V1a Receptor in Orexin/Hypocretin Neurons: Implications for Water Homeostasis

“…Orexin/YC2.1 mice Yamanaka et al, 2006) were used for calcium imaging of orexin neurons. Orexin/EGFP mice (Yamanaka et al, 2003a,b) were used for whole-cell recordings.…”

“…Orexin neurons receive abundant inputs from the limbic system, the raphe nucleus, and the basal forebrain Yoshida et al, 2006). Intracellular calcium in orexin neu-rons is altered by a number of neuroactive substances, including cholecystokinin, neurotensin, AVP, oxytocin, neuropeptide Y (NPY), adenosine, serotonin, and noradrenaline (Fu et al, 2004;Tsujino et al, 2005;Yamanaka et al, 2006;Liu and Gao, 2007).…”

Cholinergic Regulation of Orexin/Hypocretin Neurons Through M3 Muscarinic Receptor in Mice

“…During recordings, cells were superfused with extracellular physiological solution containing 140 mM NaCl, 2 mM KCl, 1 mM CaCl 2 , 1 mM MgCl 2 , 10 mM HEPES, and 10 mM glucose (pH 7.4). Designated concentrations of CCh were dissolved in HEPES-buffered solution and applied locally through a thin polyethylene tube positioned near recording cells as previously described (16,17,20,22). Designated concentrations of antagonists were applied in the perfusion solution.…”

“…Sections were prepared from mouse brains as previously described (20,23). We used an anti-choline acetyl transferase (ChAT) goat polyclonal antibody (diluted 1:100) (16) and an anti-orexin rabbit antibody (diluted 1:1000) (2).…”