Synaptic transmission: Not a one-way street

The mossy fiber synapse is crucial for information storage in the neuronal network. Synaptic transmission is plastic meaning that a variable amount of chemical signal, the so-called neurotransmitter, is released into the synapse. To understand the mechanism of plasticity at work in this synapse, Okamoto precisely stimulated the pre-synaptic terminal of the mossy fiber synapse in rats and at the same time recorded from the post-synaptic neuron. "We need to know the synapse's exact properties -- with the numerical values, e.g., for its conductance -- to create an exact model of this synapse. With his exact measurements, Yuji managed to obtain these numbers," adds Peter Jonas, co-corresponding author with postdoc David Vandael.

Smart teacher reacts to overloaded student

Unexpectedly, the researchers found that the post-synaptic neuron influences plasticity in the pre-synaptic neuron. Previously, the mossy fiber synapse was assumed to be a "teacher synapse" that induces firing in the post-synaptic neuron. "Instead, we find that this synapse acts like a 'smart teacher', who adapts the lessons when students are overloaded with information. Similarly, the pre-synaptic mossy fiber detects when the post-synaptic neuron can't take more information: When activity increases in the post-synaptic neuron, the pre-synaptic neuron reduces the extent of plasticity," explains Jonas.

This finding raises the question of how the post-synaptic neuron sends information about its activity status to the pre-synaptic neuron. Pharmacological evidence points to a role for glutamate, one of the key chemicals or neurotransmitters used by neurons to send signals to other cells. Glutamate is also the transmitter that is released from pre-synaptic mossy fiber terminals. When calcium levels increase in the post-synaptic neuron -- a sign that the neuron is active -- the post-synaptic neuron may release vesicles with glutamate into the synapse. The glutamate travels back to the pre-synaptic neuron against the usual flow of neuronal information. "This retrograde modulation of plasticity likely helps to improve information storage in the downstream hippocampal network," says Jonas, and he adds: "Once again, exact measurements have shown that reality is more complex than a simplified model would suggest."