New Clues to the Processing of Memories

PASADENA, Calif.- Quick! Memorize this sentence: The temporoammonic (TA) pathway is a entorhinal cortex (EC) input that consists of axons from layer III EC neurons that make synaptic contacts on the distal dendrites of CA1 neurons.

If by chance you can't memorize this, say two researchers from the California Institute of Technology, it may be due to this very TA pathway that is modulating what your brain remembers.

In another clue toward understanding the processing of memories, graduate student Miguel Remondes and Erin M. Schuman, an associate professor of biology at Caltech and an assistant investigator of the Howard Hughes Medical Institute, have now gleaned two possible roles for the TA pathway that until now were not known. The research is reported in the April 18 issue of the journal Nature.

Using rat hippocampal slices, they've found that this pathway may be part of the brain's decision-making process about whether to keep a particular input and form a memory, or reject it.

Input from the senses—an odor, a sight, or a sound, say, is first received by the brain's cortex. Then, via a specific pathway of nerve fibers long known to scientists, the signals are sent on to the hippocampus. That organ processes the signals, then sends them back to the cortex, probably for long-term storage.

Scientists have also known about the TA pathway, but not its function. Now Remondes and Schuman report that the TA pathway may serve as a memory gatekeeper that can either enhance or diminish the signals of the specific set of neurons that form a memory. Further, they've shown that this pathway may also provide the hippocampus with the information it needs to form so-called place-selective cells; that is, cells that help animals to know where they are in their environments.

The hippocampal formation comprises several structures in the brain and includes the seahorse-shaped hippocampus and a second organ called the dentate gyrus. The formation is involved in saving and retrieving long-term memories. Scientists divide the hippocampus into four divisions, from CA1 to CA4. CA1 and CA3 play major roles in processing memory.

In their quest to understand how communication between neurons contributes to memory, scientists have focused on the "trisynaptic circuit." When input from the senses reaches the cortex, it's sent on to the dentate gyrus, then on to the hippocampus. There, the signals are serially processed by synapses in areas CA3 and CA1 of the hippocampus (synapses are gaps between two neurons that function as the site of information transfer from one neuron to another). Finally, the hippocampus sends a signal back to the cortex. That's the trisynaptic circuit.

Remondes and Schuman found that the TA pathway also sends signals. But its input comes from a different part of the cortex and goes directly to the CA1 section of the hippocampus. The TA pathway reacts depending on how close in time the synaptic signals from the hippocampus are from the original signal sent by the trisynaptic circuit. If it is close, within 40 milliseconds, the TA pathway will act as a signal (and thus a memory) enhancer; that is, it will allocate a stronger synaptic signal from the hippocampus. If it is far, more than 400 milliseconds, it will inhibit the signal.

"So the brain sends the information to the hippocampus," says Remondes, "and instead of just collecting the result of its activity, the hippocampus may very well perform 'quality control' on the potential memory. And it may be doing this by using the direct cortical input from the TA pathway." Perhaps, then, this is a further clue to how memories are stored—or forgotten.

In addition, although the scientists have not done any specific spatial memory experiments, their work may have relevance to how the brain forms place-selective cells. Since other studies previously established that the trisynaptic circuit is not necessary for spatial memory, some of the important information entering the hippocampus may actually be provided by the TA pathway.

"The TA pathway has been briefly described in the past, but not really acknowledged as a 'player' in the memory debate," says Remondes. "Hopefully, these findings will bring new insight into how we form, or don't form, memories."