Figure 1.

States and transitions of the synapse model. Potentiating protocols applied to the model have different outcomes. A, Schematic view of the different synaptic states. On the left is a sketch of the low state of a synapse. It consists of three elements, a weak weight (blue) and two hidden variables, the tagging-related variable T (gray), currently in its lower state, and a small scaffold (red). The diagram focuses on potentiation from the low to the high state. The synapse's internal variables are represented by three double well potentials (blue, gray and red curves). These variables are coupled to each other (shown by large arrows), which alters their stability properties. A variable in its low state is represented by a ball on the left side of a panel and a variable in its high state by a ball on the right side. The directions of the couplings depend on the synapse state and on its recent history. In the low state, all three variables are in the lower potential well and the couplings are upstream, from the scaffold to the tagging variable T and from T to the weight. A potentiating plastic event carries the weight to its strong state (w = +1) without affecting the two other layers. It also reverses the coupling from the weight to T. The synapse exhibits then initial LTP. After LTP induction, within ∼10 min, a tag is set (T = +1) due to the influence of the first layer on the second (filled blue arrow). The coupling between the first two layers then comes back to its resting direction from bottom to top. If an appropriate neuromodulation (e.g., dopamine) is delivered to the postsynaptic neuron, production of PRP is triggered, allowing for stabilization of recent plastic changes. It reverses the direction of the coupling between T and the scaffold for ∼2 h, enabling the last layer to follow its neighbor to the large state (z = +1). This changes the long-term stability of the synapse. In the absence of external input, a tagged synapse decays back to its resting state within a few hours. The timescale of the decay is determined by the time needed for noise to push T out of the metastable potential well. When a depotentiating protocol is applied to a tagged synapse, the weight is reset to its weak state. Both the first and second layer are then in a metastable situation. Because the potential barrier for the weight is lower than for T, the weight will bounce back up, setting the synapse back into the e-LTP state. It allows either for capture of PRPs if there was any dopamine release or for decay to the synapse's low state. This stands in contrast to the case in which depotentiation occurs before a tag had time to be set. In this situation, the synapse is directly set back to the low state. On the right of the diagram is a sketch of the high state of a synapse. In contrast to the sketch on the left, the weight is strong, T is up, and the scaffold is large. B, Sketch of a postsynaptic neuron and of its incoming synapses. The upper synapse's state corresponds to the one in A directly above. A synapse can be in the low state (small black triangle), in the i-LTP state (large blue triangle), in the e-LTP state (blue triangle and gray flag), or in the high state (blue triangle filled in red). Consolidation occurs through the presence of PRPs (green circles). C, Typical behavior of a synapse during an e-LTP-inducing protocol. We show the time course of the three layers of a synapse (blue, gray, and red lines) and the synaptic state to which it corresponds. D, As in C, but with a stronger stimulus-inducing l-LTP. Note that consolidation occurs because of the presence of PRPs. E, As in C, with a resetting stimulus 15 min after the start of potentiation.