Posterior hypothalamic nucleus serotonin depletion facilitates spatial learning and increases power and coherence in the posterior hypothalamic-septal-hippocampal circuit in rat.

Serotonin (5-HT), which is produced in the raphe nuclei and innervates different relays of the synchronizing ascending system, was proposed to desynchronize hippocampal theta activity. Serotonin reduction in the hippocampus (HCP) and medial septum (MS) increases the expression of theta activity and facilitates spatial learning. However, its reduction in both the supramammillar nucleus (SuMn) and posterior hypothalamic nucleus (PHn), or, in the SuMn alone, induces a reduction in hippocampal theta expression, alters coherence in the SuMn-MS-HCP circuit, and, is associated with deficient place learning. Thus, 5-HT influences theta activity and learning at several relays in the synchronizing ascending system (SAS). It has been suggested that PHn modulates both frequency and amplitude, and its output reaches the MS, which is the pacemaker for hippocampal theta activity. The release of 5-HT in PHn from median raphe neurons may be a factor in modulating hippocampal theta activity and learning. To evaluate this hypothesis, 5-HT was reduced in PHn via an infusion of 5,7-Dihydroxytriptamine, and theta activity was registered in the PHn, MS, dentate gyrus (DG), and CA1 during place learning. The rats were subjected to Morris's maze training with simultaneous recording of the field potential for six consecutive days. Power and coherence were compared by group, behavioral condition (baseline and platform searching), and frequency (4-12 Hz). The reduction in 5-HT, verified via HPLC, facilitated place learning concomitant with an increase in power and coherence in the PHn-MS-HCP circuit. Higher power and decreased coherence occurred in four rats with increased 5-HT in the PHn (via a putative partial lesion of serotonergic axons), along with place learning deficiency. In conclusion, serotonin modulates spatial learning by acting on the PHn and modulating both coherence and amplitude of hippocampal theta activity.