Short-term synaptic plasticity at the mossy fiber synapse of the rodent hippocampus

Abstract

Synaptic short- and long-term plasticity are key mechanisms by which neuronal ensembles store information. The mossy fiber synapse (MF-CA3 synapse) is formed by axons of dentate gyrus granule cells and exhibits a striking form of short-term plasticity that is distinct from most other synapses in the CNS. Stimulation of mossyfiber axons at low frequencies (0.1 - 10 Hz) causes a dramatic increase in glutamate release at the MF-CA3 synapse, and a concomitant augmentation of the excitatory postsynaptic potentials. This phenomenon is called frequency facilitation. The mechanisms of <i>frequency facilitation</i> are currently under discussion.<br /> We therefore tested the role of Ca²⁺ in the mediation of frequency facilitation at MF-CA3 synapses and found frequency facilitation independent of an accumulation of bulk Ca²⁺. We tested the effect of blocking N- and P/Q-type voltage gated Ca²⁺ channels on frequency facilitation and found both channels contributing equally to the expression of frequency facilitiaton.<br /> Because of the complex behavior of frequency facilitation from the extracellular Ca²⁺ concentration, we tested different mathematical models to explain this form of plasticity. A model with two distinct Ca²⁺ sensors, one responsible for basal transmitter release while the other one causes facilitation of release, described best our data.<br /> We furthermore tested the role of different signalling pathways that are known to affect transmitter release and other forms short-term plasticity. Facilitation was unaltered in mice lacking functional αCamKII, or following application of CamKII blockers. It was also unaffected by inhibition of protein kinase A (PKA), protein kinase C (PKC), mitogen-activated protein kinase (MAPK), phosphatases, Kainate receptors (KARs), phosphatidyl-inositol kinase 3 and 4 (PI-3 and PI-4 kinase), and agents affecting the integrity of the cytoskeleton.<br /> These data suggest that frequency facilitation is either mediated by signalling cascades that are distinct from the ones tested in this study, or alternatively, they are consistent with a more direct Ca²⁺-dependent mechanism acting directly on the release machinery.