In vivo contribution of h-channels in the septal pacemaker to theta rhythm generation

One of the most intriguing network-level inferences made on the basis of in vitro and modelling data regarding the role of I-h current was that they participate in rhythmogenesis in different parts of the brain. The nature of I-h contribution to various neuronal oscillations is far from uniform however, and the proper evaluation of the role of I-h in each particular structure requires in situ investigations in the intact brain. In this study we tested the effect of I-h blockade in the medial septum on hippocampal theta rhythm in anaesthetized and freely behaving rats. We could not confirm the recent report of elimination of theta by septal injection of ZD7288 [C. Xu et al. (2004) Eur. J. Neurosci., 19, 2299-2309]; the observed effects were more subtle and more specific. We found that I-h blockade in the medial septum substantially decreased the frequency of hippocampal oscillations without changing the context in which theta occurred, i.e. specific behaviours in freely moving rats and spontaneous switching and brainstem stimulation under anaesthesia. Septal injection of ZD7288 eliminated atropine-resistant theta elicited by high intensity electrical stimulation of the reticular formation in anaesthetized rats but was ineffective in combination with the muscarinic agonist, carbachol. Thus, functional I-h was necessary for the septum to generate or transmit high frequency theta rhythm elicited by strong ascending activation, whereas low frequency theta persisted after I-h blockade. These results suggest that I-h plays a specific role in septal theta generation by promoting fast oscillations during exploratory behaviour and rapid eye movement sleep.