To study a complex human behavior, such as remembering appropriate information at the right time, Eichenbaum had to train rats to memorize an important piece of information and then find a way for them to use it. So his team trained rats to find Froot Loops in flowerpots. “Rats are absolutely nuts about Froot Loops,” he says.

For example, the rats learned that in room A the cereal is hidden in a pot filled with purple plastic beads that smell sweet. But in room B, the goods are in the pot filled with black paper shreds that smell spicy. “Rats are great with odors and textures, so we’re using textural and olfactory cues to direct them to express their memory,” says Eichenbaum.

As the rats navigate from room to room, Eichenbaum’s team records their brain activity using electrodes inserted into the brain. They monitor both the hippocampus, known to be the seat of memory in the brain, and the prefrontal cortex, thought to be a coordinator.

diagram showing flow of memory information in a rat brain The circuitry that guides the selection of memories based on the current context spans the rat brain. Information flows from the ventral hippocampus (vHPC), in the lower part of the brain, to the prefrontal cortex (mPFC), and then back to the dorsal hippocampus (dHPC), near the top of the brain. Breakdowns in the circuitry can cause different types of memory problems, including loss of memory and also the inability to determine which memories are appropriate for the current situation. Diagram courtesy of Howard Eichenbaum In previous studies, the team had already learned that neurons in the prefrontal cortex fire in relation to cues that signal rewards, such as a particular pot that contains a stash of Froot Loops. They had also identified neurons in a region called the ventral hippocampus that recognize the room the rat is in. Neurons in the dorsal hippocampus fire when the rat recognizes a flowerpot it has seen before. In this most recent experiment, they learned how the brain puts these pieces of information together to guide a decision, like which pot to dig in.

For instance, when the rat enters room A, the ventral hippocampus transmits to the prefrontal cortex, setting the context to room A. The dorsal hippocampus begins firing as it recognizes flowerpots. The prefrontal cortex, which knows that the reward in room A is in the pot with purple beads, sends this information to the dorsal hippocampus, telling it which memory to act on. “The two regions operate together as a system, kind of like handshaking,” says Eichenbaum. “We’re seeing at the level of neurons what happens in cognitive life.”