Elsevier

Neuroscience

Volume 108, Issue 2, 10 December 2001, Pages 177-181
Neuroscience

Letter to Neuroscience
Orexins/hypocretins excite basal forebrain cholinergic neurones

https://doi.org/10.1016/S0306-4522(01)00512-7Get rights and content

Abstract

The orexins (orexin A and B, also known as hypocretin 1 and 2) are two recently identified neuropeptides (de Lecea et al., 1998, Sakurai et al., 1998) which are importantly implicated in the control of wakefulness (for reviews see Hungs and Mignot, 2001, Kilduff and Peyron, 2000, Sutcliffe and de Lecea, 2000, van den Pol, 2000, Willie et al., 2001). Indeed, alteration in these peptides’ precursor, their receptors or the hypothalamic neurones that produce them leads to the sleep disorder narcolepsy (Chemelli et al., 1999, Lin et al., 1999, Peyron et al., 2000, Thannickal et al., 2000). The mechanisms by which the orexins modulate wakefulness, however, are still unclear. Their presence in fibres coursing from the hypothalamus (Peyron et al., 1998) up to the preoptic area (POA) and basal forebrain (BF) suggests that they might influence the important sleep and waking neural systems situated there (Jones, 2000). The present study, performed in rat brain slices, demonstrates, however, that the orexins have no effect on the GABA sleep-promoting neurones of the POA, whereas they have a strong and direct excitatory effect on the cholinergic neurones of the contiguous BF. In addition, by comparing the effects of orexin A and B we demonstrate here that orexins’ action depends upon orexin type 2 receptors (OX2), which are those lacking in narcoleptic dogs (Lin et al., 1999). These results suggest that the orexins excite cholinergic neurones that release acetylcholine in the cerebral cortex and thereby contribute to the cortical activation associated with wakefulness.

Section snippets

Experimental procedures

The optimal slices for recording were chosen according to published atlases for the VLPO (Sherin et al., 1998) and the MCPO (Gritti et al., 1993) in the rat. Coronal brain slices (300–400 μm thick) were obtained from young rats (15–20 days, provided by the animal facility of the Geneva Medical Center and treated according to the Swiss Federal Veterinary Office). They were incubated at room temperature in artificial cerebrospinal fluid (ACSF) which contained (in mM): NaCl 130, KCl 5, KH2PO4

Acknowledgements

This study was supported by grants from the Swiss Fonds National to M.M. and M.S., the Canadian Medical Research Council to B.E.J. and a Roche fellowship to L.B.

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