GABAB and CB1 cannabinoid receptor expression identifies two types of septal cholinergic neurons

Septohippocampal cholinergic neurons play key roles in learning and memory processes, and in the generation of hippocampal theta rhythm. The range of receptors for endogenous modulators expressed on these neurons is unclear. Here we describe GABAB 1a/b receptor (GABABR) and type 1 cannabinoid receptor (CB1R) expression in rat septal cholinergic [i.e. choline acetyltransferase (ChAT)-positive] cells. Using double immunofluorescent staining, we found that almost two-thirds of the cholinergic cells in the rat medial septum were GABABR positive, and that these cells had significantly larger somata than did GABABR-negative cholinergic neurons. We detected CB1R labelling in somata after axonal protein transport was blocked by colchicine. In these animals about one-third of the cholinergic cells were CB1R positive. These cells again had larger somata than CB1R-negative cholinergic neurons. The analyses confirmed that the size of GABABR-positive and CB 1R-positive cholinergic cells were alike, and all CB 1R-positive cholinergic cells were GABABR positive as well. CB1R-positive cells were invariably ChAT positive. All retrogradely labelled septohippocampal cholinergic cells were positive for GABABR and at least half of them also for CB1R. These data shed light on the existence of at least two cholinergic cell types in the medial septum: one expresses GABABR and CB1R, has large somata and projects to the hippocampus, whereas the other is negative for GABABR and CB1R and has smaller somata. The results also suggest that cholinergic transmission in the hippocampus is fine-tuned by endocannabinoid signalling.