Hypocretin and nicotine excite the same thalamocortical synapses in prefrontal cortex: correlation with improved attention in rat.
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.
Lambe
Evelyn K
EK
Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut 06508, USA. evelyn.lambe@yale.edu
Olausson
Peter
P
Horst
Nicole K
NK
Taylor
Jane R
JR
Aghajanian
George K
GK
D000200:Action Potentials / Q000187:drug effects; D000344:Afferent Pathways / Q000187:drug effects; D000818:Animals; D000831:Animals, Newborn; D001288:Attention / Q000187:drug effects*; D001522:Behavior, Animal; D002118:Calcium / Q000494:pharmacology; D003952:Diagnostic Imaging / Q000379:methods; D066298:In Vitro Techniques; D047908:Intracellular Signaling Peptides and Proteins / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects; D009479:Neuropeptides / Q000494:pharmacology*; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D000068797:Orexins; D017785:Photons; D017397:Prefrontal Cortex / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000187:drug effects*; D013788:Thalamus / Q000166:cytology
D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D018722:Nicotinic Agonists; D000068797:Orexins; D009538:Nicotine; D002118:Calcium