Hippocampal serotonin depletion facilitates place learning concurrent with an increase in CA1 high frequency theta activity expression in the rat

Acetylcholine- and serotonin-dependent theta activities have been long proposed to exist. However, several studies have shown that serotonin tends to desynchronise hippocampal EEG activity. Theta activity has been related to the processing of hippocampal place learning. Since the serotonergic system can influence hippocampal theta activity, it could function as a modulator of spatial learning. For these reasons, we investigated the possible role of hippocampal serotonin in the regulation of theta activity during the acquisition of map-based spatial information. Following 5-HT hippocampal depletion through 5,7-dihydroxytriptamine-induced lesions to the fimbria, fornix and cingulate bundle of adult rats, CA1 hippocampal theta activity was recorded during place learning training. Only rats with reduction higher than 90% from controls, verified post-mortem by HPLC were studied. A facilitation of place learning after hippocampal serotonin depletion occurred, and was associated with earlier expression of dominant high frequency theta activity (6.5–9.5 Hz). Therefore, theta activity was related to the accuracy of behavioural performance through 5-HT modulation in a place learning test.