RESUMEN
It is widely known that hypocretins are essential for the regulation of wakefulness. Our recent reports have found that hypocretin-1 shows a direct postsynaptic excitatory effect on rat prefrontal cortex (PFC) pyramidal neurons. It remains unclear whether hypocretin-1 may interact with two classical neurotransmitter systems, glutamate and gamma-aminobutyric acid (GABA) in rat PFC. For this reason, we here investigated the modulatory actions of hypocretin-1 with these two transmitters on freshly isolated PFC pyramidal neurons using whole-cell patch-clamp recordings. We found that coadministration of hypocretin-1 and glutamate showed a synergistic effect on the recorded cells, and hypocretin-1 could excite the neurons even if GABA was present. Thus, our data suggest that there may be hypocretin-glutamate and hypocretin-GABA interactions in the PFC.
Asunto(s)
Lóbulo Frontal/fisiología , Ácido Glutámico/fisiología , Péptidos y Proteínas de Señalización Intracelular/fisiología , Neuropéptidos/fisiología , Células Piramidales/fisiología , Ácido gamma-Aminobutírico/fisiología , Potenciales de Acción , Animales , Lóbulo Frontal/citología , Ácido Glutámico/farmacología , Técnicas In Vitro , Péptidos y Proteínas de Señalización Intracelular/farmacología , Neuropéptidos/farmacología , Orexinas , Técnicas de Placa-Clamp , Células Piramidales/efectos de los fármacos , Ratas , Ratas Wistar , Ácido gamma-Aminobutírico/farmacologíaRESUMEN
We have investigated the direct excitatory effects of hypocretin-1 on acutely isolated prefrontal cortical pyramidal neurons and explored the signaling mechanisms of these actions. Puff application of hypocretin-1 caused an excitation in the recorded neurons. These effects of hypocretin-1 were abolished by a phospholipase C inhibitor D609, demonstrating that phospholipase C mediates the actions of hypocretin-1. A specific protein kinase C inhibitor, bisindolylmaleimide II, blocked the excitatory actions of hypocretin-1, suggesting that protein kinase C plays a key role. Finally, protein kinase A inhibitor applied intracellularly did not affect the responses. These results indicate that hypocretin-1 excites prefrontal neurons by activation of phospholipase C and protein kinase C pathways, but not protein kinase A.