The opioid peptide dynorphin mediates heterosynaptic depression of hippocampal mossy fibre synapses and modulates long-term potentiation.

The mossy fibre pathway in the hippocampus uses glutamate as a neurotransmitter, but also contains the opioid peptide dynorphin. Synaptic release of dynorphin causes a presynaptic inhibition of neighbouring mossy fibres and inhibits the induction and expression of mossy fibre long-term potentiation. These findings demonstrate a physiological role for a neuropeptide in the central nervous system, provide a functional basis for the coexistence of a neuropeptide with classic neurotransmitters and demonstrate the very different roles played by these two classes of signalling molecules.