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The Journal of Neuroscience, July 28, 2004, 24(30):6760-6764; doi:10.1523/JNEUROSCI.1783-04.2004

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BRIEF COMMUNICATION
Exclusive Postsynaptic Action of Hypocretin-Orexin on Sublayer 6b Cortical Neurons

Laurence Bayer,¹ Mauro Serafin,¹ Emmanuel Eggermann,¹ Benoît Saint-Mleux,¹ Danièle Machard,¹ Barbara E. Jones,² and Michel Mühlethaler¹

¹Département de Physiologie, Centre Médical Universitaire, 1211 Genève 4, Switzerland, and ²Department of Neurology and Neurosurgery, McGill University, Montreal Neurological Institute, Montreal, Quebec, Canada H3A 2B4

The hypocretin-orexin (hcrt-orx) neurons are thought to maintain wakefulness because their loss results in narcolepsy. This role may be fulfilled by the excitatory action that the hcrt-orx peptide exerts on multiple brainstem and forebrain systems that, in turn, promote cortical activation. Here, we examined whether hcrt-orx may also exert a postsynaptic excitatory action at the level of the cortex, where hcrt-orx fibers project. However, we found that neurons in layers 2-5 in the primary somatosensory cortex (SSp) were unresponsive to hcrt-orx. We then found that although all neurons tested in sublayer 6a were also unresponsive to hcrt-oxr, all those tested in sublayer 6b were highly sensitive to the peptide. The sublayer selectivity of hcrt-oxr was not restricted to the somatosensory cortex, because it was also found to be present in the primary visual cortex, the motor cortex, and the cingulate cortex. In the SSp, in which the hcrt-oxr effect was investigated further, it was demonstrated to be postsynaptic, to result from an interaction with Hcrtr2-OX₂ receptors and to depend on the closure of a potassium conductance. Similar to the selectivity of action in the thalamus, where hcrt-oxr excites the nonspecific thalamocortical projection neurons and not the specific sensory relay neurons, here in the cortex, it excites a specific subset of cortical neurons which, through corticocortical projections, may also be involved in promoting widespread cortical activation.

Key words: arousal; cortex; hypocretin; orexin; sleep; waking

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Received June 27, 2003; revised June 11, 2004; accepted June 13, 2004.

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