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The Journal of Neuroscience, May 25, 2005, 25(21):5225-5229; doi:10.1523/JNEUROSCI.0719-05.2005
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BRIEF COMMUNICATION
Hypocretin and Nicotine Excite the Same Thalamocortical Synapses in Prefrontal Cortex: Correlation with Improved Attention in Rat
Evelyn K. Lambe,1 Peter Olausson,1 Nicole K. Horst,2 Jane R. Taylor,1 andGeorge K. Aghajanian1,3 1Department of Psychiatry, 2Interdepartmental Neuroscience Program, and 3Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06508
Thalamic projections to prefrontal cortex are important for executive aspects of attention. Using two-photon imaging in prefrontal brain slices, we show that nicotine and the wakefulness neuropeptide hypocretin (orexin) excite the same identified synapses of the thalamocortical arousal pathway within the prefrontal cortex. Although it is known that attention can be improved when nicotine is infused directly into the midlayer of the prefrontal cortex in the rat, the effects of hypocretin on attention are not known. The overlap in thalamocortical synapses excited by hypocretin and nicotine and the lack of direct postsynaptic effects prompted us to compare their effects on a sustained and divided attention task in the rat. Similar to nicotine, infusions of hypocretin-2 peptide into the prefrontal cortex significantly improved accuracy under high attentional demand without effects on other performance measures. We show for the first time that hypocretin can improve attentional processes relevant to executive functions of the prefrontal cortex.
Key words: two-photon; orexin; divided attention; rat;
4
2 nicotinic acetylcholine receptors; behavior
Received Feb 22, 2005; revised April 19, 2005; accepted April 20, 2005.
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