Glutamatergic projection from the nucleus incertus to the septohippocampal system

Recent findings support a relevant role of the nucleus incertus in the control of the hippocampal activity through the modulation of theta rhythm. Previous studies from our group have shown that this nucleus is a critical relay between reticularis pontis oralis and the medial septum/diagonal band, regarded as the main activator and the pacemaker of the hippocampal oscillations, respectively. Besides, the nucleus incertus is highly linked to activated states related to the arousal response.The neurotransmission of the nucleus incertus, however, remains uncertain. Only GABA and the neuromodulator relaxin 3 are usually considered to be involved in its contribution to the septohippocampal system. In this work, we have analyzed the existence of an excitatory projection from the nucleus incertus to the medial septum. We have found a group of glutamatergic neurons in the nucleus incertus projecting to the medial septum. Moreover, we were able to describe a segregated distribution of calbindin and calretinin neurons. While calretinin expression was restricted to the nucleus incertus pars compacta, calbindin positive neurons where observed both in the pars dissipata and the pars compacta of the nucleus.The present work provides innovative data supporting an excitatory component in the pontoseptal pathway.

► We describe a glutamatergic projection from the nucleus incertus to medial septum.
► A segregated distribution of calbindin and calretinin neurons is distinguishable.
► Calbindin expression was restricted to the nucleus incertus pars dissipata.
► Calretinin expression was observed both in the pars dissipata and the pars compacta.