Reverse replay of hippocampal place cells occurs frequently at rewarded locations, suggesting its contribution to goal-directed path learning. Symmetric spike-timing dependent plasticity (STDP) in CA3 likely potentiates recurrent synapses for both forward (start to goal) and reverse (goal to start) replays during sequential activation of place cells. However, how reverse replay selectively strengthens forward synaptic pathway is unclear. Here, we show computationally that firing sequences bias synaptic transmissions to the opposite direction of propagation under symmetric STDP in the co-presence of short-term synaptic depression or afterdepolarization. We demonstrate that significant biases are created in biologically realistic simulation settings, and this bias enables reverse replay to enhance goal-directed spatial memory on a W-maze. Further, we show that essentially the same mechanism works in a two-dimensional open field. Our model for the first time provides the mechanistic account for the way reverse replay contributes to hippocampal sequence learning for reward-seeking spatial navigation.
To find their way around, animals – including humans – rely on an area of the brain called the hippocampus. Studies in rodents have shown that certain neurons in the hippocampus called place cells become active when an animal passes through specific locations. At each position, a different set of place cells fires. A journey from A to B will thus be accompanied by a sequential activation of place cells corresponding to a particular point.
Rats can learn new routes to a given place. Every time they take a specific way, the connections between the activated place cells become stronger. After learning, the hippocampus replays the sequence of place cell activation both in the order the rat has experienced and backwards. This is known as reverse replay, which occurs more often when the animals find rewards at their destination. This suggests that reverse replay may help animals learn the routes to locations where food is available.
To test this idea, Haga and Fukai built a computer model that simulates the hippocampal activity seen in a rat running through a maze. In contrast to previous models, which featured only forward replay, the new simulation also included reverse replay. The results confirmed that reverse replay helps the rodents to learn routes to rewarded locations. It also enables the hippocampus to combine multiple past experiences, which may teach animals that a combination of previous paths will lead to a reward, even if they have never tried the combined route before.
The hippocampus has a central role in many different types of memory. The findings by Haga and Fukai may therefore provide a framework for studying the mechanisms of memory and decision-making. The results could even offer insight into the mechanisms of logical thinking. After all, the ability to combine multiple known paths into a new route bears some similarity to joining up thought processes such as ‘If Sophie oversleeps, she will miss the bus’ with ‘If Sophie misses the bus, she will be late for school’ to reason that ‘If Sophie oversleeps, she will be late for school’. Future studies should test whether reverse replay helps with this process of deduction.