Hypocretin/Orexin Receptor Functions in Mesopontine Systems Regulating Sleep, Arousal, and Cataplexy

Orexin/hypocretin receptor signalling: a functional perspective

“…Similarly in rat dorsal raphé nucleus, mRNA for both orexin receptors are co‐distributed (Trivedi et al ., ; Marcus et al ., ) and can be recovered from the same cells (Brown et al ., ). Orexin‐A and orexin‐B activate a NSCC with a similar potency in rat (Brown et al ., ; Liu et al ., ; Soffin et al ., ) but recordings from slices made from OX 1 and OX 2 knockout mice indicate that either receptor is sufficient to mediate the NSCC current (Leonard et al ., ).…”

“…Orexins depolarize neurons in many of the structures that are efferent targets of the ventral tegmental area system including neurons in the shell region of the nucleus accumbens via OX 2 (Mukai et al ., ), the bed nucleus of the stria terminals (Lungwitz et al ., ) and neurons that provide input to the nucleus accumbens, including the central nucleus of the amygdala via OX 2 receptors (Bisetti et al ., ), paraventricular thalamic nucleus (Ishibashi et al ., ; Huang et al ., ; Kolaj et al ., ; Doroshenko and Renaud, ; Zhang et al ., 2009; 2010) and prefrontal cortex (Li et al ., ; Yan et al ., ). Orexins also depolarize neurons in structures that provide afferent input to the ventral tegmental area including laterodorsal tegmentum (Burlet et al ., ; Kohlmeier et al ., 2004; 2008; Leonard et al ., ; Ishibashi et al ., ; Takahashi et al ., ) and pedunculopontine tegmentum (Kim et al ., 2009a; 2009b) via OX 1 receptors.…”

“…In the control of arousal and behavioural state, orexin actions have been identified at many cell groups thought to be important for maintaining arousal including the orexin neurons themselves (Yamanaka et al ., ) and all tested ascending cholinergic systems (Eggermann et al ., ; Burlet et al ., ; Wu et al ., 2002; 2004; Hoang et al ., ; Kohlmeier et al ., 2004; 2008; Arrigoni et al ., ; Leonard et al ., ) and monoaminergic systems (Hagan et al ., ; Horvath et al ., ; Ivanov and Aston‐Jones, ; Nakamura et al ., ; Bayer et al ., ; Brown et al ., 2001; 2002; Eriksson et al ., ; Uramura et al ., ; Liu et al ., ; van den Pol et al ., ; Yamanaka et al ., ; Hoang et al ., ; Willie et al ., ; Kohlmeier et al ., 2004; 2008; Korotkova et al ., ; Soffin et al ., ; Haj‐Dahmane and Shen, ; Murai and Akaike, ; Borgland et al ., ; Leonard et al ., ; Mochizuki et al ., ; Ishibashi et al ., ) which form part of the ascending reticular activating system and project to the thalamus and/or cortex (for review, see Jones, ). Moreover, orexins excite neurons in the sublaterodorsal region (Brown et al ., 2006; 2008), which is an area containing neurons with multiple transmitter phenotypes, and recently recognized as critical in regulating rapid eye movement sleep expression and muscle tone during sleep (Boissard et al ., ; Lu et al ., ).…”