SUPER-DETONATION AT HUMAN HIPPOCAMPAL MOSSY FIBER SYNAPSES

The hippocampus is essential for learning and memory, and the mossy fiber synapse is a key connection of its trisynaptic circuit. In rodents, this synapse acts as a conditional detonator, where single excitatory postsynaptic potentials (EPSPs) are subthreshold, but can become suprathreshold in conjunction with plasticity. This ‘teacher signal’ is thought to provide input that can be associated and stored in the CA3 recurrent network. However, the properties of the mossy fiber synapse have been predominantly studied in rodents, and whether it plays the same role in other species, including humans, is unknown. To address this question, we performed subcellular paired recordings between presynaptic mossy fiber boutons and postsynaptic CA3 pyramidal neurons in non-sclerotic human brain tissue resected from temporal lobe epilepsy patients. Analysis of unitary synaptic transmission revealed that single stimuli evoked suprathreshold EPSPs, triggering postsynaptic action potentials with high probability (83% in human vs. 8.2% in mouse, 3 and 7 pairs respectively). Suprathreshold amplitudes were maintained during repetitive stimulation, resulting in burst-to-burst synaptic transmission. Moreover, at the single-cell level, individual CA3 cells received ~5 times more mossy fiber input in humans than in mice, while overall mossy fiber connectivity was sparser. Together, the distinct properties of mossy fiber synapses we observe in human tissue may contribute to the computational power of our own hippocampus.