The hippocamposeptal pathway generates rhythmic firing of GABAergic neurons in the medial Septum and diagonal bands:: An investigation using a complete septohippocampal preparation in vitro

The medial septum diagonal band area ( MS/DB) projects to the hippocampus through the fornix/ fimbria pathway and is implicated in generating hippocampal theta oscillations. The hippocampus also projects back to the MS/ DB, but very little is known functionally about this input. Here, weinvestigated the physiological role of hippocamposeptal feedback to the MS/ DB in a complete in vitro septohippocampal preparation containing the intact interconnecting fornix/ fimbria pathway. We demonstrated that carbachol-induced rhythmic thetalike hippocampal oscillations recorded extracellularly were synchronized with powerful rhythmic IPSPs in whole-cell recorded MS/ DB neurons. Interestingly, we found that these IPSPs evoked rebound spiking in GABAergic MS/ DB neurons. In contrast, putative cholinergic and glutamatergic MS/ DBneurons responded only weakly with rebound spiking and, as a result, were mostly silent during theta-like oscillations. We next determined the mechanism underlying the rebound spiking that followed the IPSPs in MS/ DB GABAergic neurons using phasic electrical stimulation of the fornix/ fimbria pathway. We demonstrate that the increased rebound spiking was attributable to the activation of I-h current, because it was significantly reduced by low concentrations of the Ih antagonist ZD7288 [ 4-( N- ethyl- Nphenylamino)1,2- dimethyl- 6-( methylamino) pyridinium chloride]. Together, these results suggest that rhythmical activity in hippocampus is transferred to the MS/ DB and can preferentially phase the spiking of GABAergic MS/ DB neurons because of their significant expression of Ih currents. Our data demonstrate that hippocamposeptal inhibition facilitates theta rhythmic discharges in MS/ DB GABAergic neurons while favoring the inhibition of most ACh and glutamate neurons.