SUMMARY
The hippocampal mossy fiber synapse is a key synapse of the trisynaptic circuit of the hippocampus. Post-tetanic potentiation (PTP) is the most powerful form of plasticity at this synaptic connection. It is widely believed that mossy fiber PTP is an entirely presynaptic phenomenon, implying that PTP induction is input-specific, and requires neither activity of multiple inputs nor stimulation of postsynaptic neurons for induction. Thus, mossy fiber PTP appears to lack cooperativity and associativity that characterize other forms of plasticity. To directly test these predictions, we made paired recordings between single mossy fiber terminals and postsynaptic CA3 pyramidal neurons in rat brain slices. By stimulating parallel but non-overlapping mossy fiber bouton (MFB) inputs converging onto single CA3 neurons, we confirmed that PTP was inputspecific and non-cooperative. Unexpectedly, mossy fiber PTP showed anti-associative induction properties. Mossy fiber excitatory postsynaptic currents (EPSCs) showed only minimal PTP after combined pre- and postsynaptic high-frequency stimulation (HFS) with intact postsynaptic Ca2+ signaling (0.1 mM EGTA), but marked PTP in the absence of postsynaptic spiking and after suppression of postsynaptic Ca2+ signaling (10 mM EGTA). PTP was rescued by blocking Ca2+ entry via voltage-gated R-type and to a smaller extent L-type Ca2+channels. PTP was also recovered by extracellular application of group II metabotropic glutamate receptor (mGluR) antagonists and vacuolar-type (v-type) H+-ATPase inhibitors, suggesting the involvement of retrograde vesicular glutamate signaling. Transsynaptic regulation of PTP induction may increase the computational power of mossy fiber synapses, and implement a break on hippocampal mossy fiber detonation.
Competing Interest Statement
The authors have declared no competing interest.