Serotonin depletion of supramammillary/posterior hypothalamus nuclei produces place learning deficiencies and alters the concomitant hippocampal theta activity in rats

• Published in: European journal of pharmacology 2012-05, Vol.682 (1-3), p.99-109
• Main Authors: Gutiérrez-Guzmán, Blanca Erika, Hernández-Pérez, J. Jesús, López-Vázquez, Miguel Ángel, Fregozo, Cesar Soria, Guevara, Miguel Ángel, Olvera-Cortés, María Esther
• Format: Article
• Language: English
• Subjects: 5,7-Dihydroxytryptamine - pharmacology; Animals; Behavior, Animal - drug effects; Behavior, Animal - physiology; CA1; CA1 Region, Hippocampal - drug effects; CA1 Region, Hippocampal - metabolism; CA1 Region, Hippocampal - physiology; Dentate gyrus; Dentate Gyrus - drug effects; Dentate Gyrus - metabolism; Dentate Gyrus - physiology; Hippocampus; Hippocampus - drug effects; Hippocampus - metabolism; Hippocampus - physiology; Hypothalamus; Hypothalamus - drug effects; Hypothalamus - metabolism; Hypothalamus - physiology; Learning; Learning - drug effects; Learning - physiology; Male; Maze Learning - drug effects; Maze Learning - physiology; Nuclei; pharmacology; Posterior hypothalamic nucleus; Rats; Rats, Sprague-Dawley; Serotonin; Serotonin - deficiency; Spatial Behavior - drug effects; Spatial Behavior - physiology; spatial discrimination; Supramammillary nucleus; Synapses; Theta activity; Theta Rhythm - drug effects; Theta Rhythm - physiology; theta rhythms
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2012.02.024

Hippocampal theta activity is important for the acquisition of spatial information and is strongly influenced and regulated by extra-hippocampal inputs from the synchronising ascending system (SAS), which includes the supramammillary nucleus (SUMn) and the posterior hypothalamic nucleus (PHn). Together these nuclei play an important role in controlling the frequency encoding of theta activity and are innervated by serotonin synapses, which also regulate theta activity and learning abilities. The participation of the SUMn in place learning and modulation of hippocampal theta activity were recently shown; thus, we questioned whether serotonin acting on SUMn/PHn could modulate place learning ability and concurrent hippocampal theta activity. The serotonergic terminals of the SUMn/PHn in rats were lesioned through 5,7-dihydroxytryptamine (5,7-DHT) infusion, and hippocampal theta activity during the Morris water maze test was recorded. Rats in the vehicle group learned the task efficiently and showed learning-related theta changes in the CA1 and dentate gyrus regions throughout the training. The 5-HT-depleted rats were deficient in the Morris water maze task and showed theta activity in the CA1 and dentate gyrus that were unrelated to the processing of learning. We conclude that serotonin can regulate the hippocampal theta activity acting on the SUMn/PHn relay of the SAS and that the influence of 5-HT in these nuclei is required for the learning-related changes in hippocampal theta activity that underlie the successful resolution of the Morris water maze task.