Multiple cannabinoid signaling cascades powerfully suppress recurrent excitation in the hippocampus
Kyle R. Jensen, Coralie Berthoux, Kaoutsar Nasrallah, Pablo E. Castillo
Abstract
Significance In the hippocampus, the recurrent excitatory circuit established by reciprocal connections between dentate granule cells and mossy cells is dynamically regulated by activity and has been implicated in pattern separation and epilepsy. The extensive projections of mossy cells make this recurrent circuit particularly prone to runaway activity. Here, we identified multiple mechanisms by which activation of cannabinoid receptors, which are highly expressed in mossy cell axons, powerfully dampen the activity of this circuit by selectively suppressing both mossy cell to granule cell basal synaptic transmission and LTP induction. These inhibitory actions likely contribute to a sparse network of quiet granule cells, which is critical to pattern separation, precludes epilepsy, and may explain some of the marijuana-mediated effects in hippocampal-dependent memory.