When we have a new experience, our brains quickly form a long-term memory of that event. The process of memory formation uses two major brain structures, the hippocampus and the entorhinal cortex (EC), which are further subdivided into sub-regions or layers that are thought to perform specialized functions relevant for the different kinds of events in our lives.
Memory neuroscientists have believed that when we recall these memories, our brains use the same hippocampal and EC circuits that were used to form the original memory. In a recent study, we surprisingly found that recalling memories recruits a “detour” brain circuit that branches off from the original memory circuit.
While most regions of the hippocampus memory
network have been well studied, the functional role of a small area called the
subiculum has been mysterious. To investigate this, we developed a novel
genetically engineered mouse line that enabled us to use light to turn off/on
subiculum neurons . By modulating the activity of subiculum neurons during a
fear-learning event, in which mice have to learn that a particular chamber is
scary, we attempted to determine whether the subiculum neurons are important for
fear learning, fear memory recall, or both.
Turning off subiculum neurons only during
fear learning had no effect on their ability to form and recall this memory. However,
in another group of mice, we observed that although these animals learned the fear
experience normally, they couldn't recall this experience when subiculum
neurons were turned off. This evidence indicated that the detour circuit
involving the subiculum – that is hippocampal CA1 to subiculum to EC layer 5 –
is necessary for memory retrieval but not memory formation. In a series of
further experiments, we found that the direct circuit from hippocampal CA1 to
EC layer 5 is necessary for memory formation but not memory retrieval. Quite
unexpectedly, we had uncovered that the output of the memory brain region, the
hippocampus (CA1), has distinct brain circuits for memory formation and
The existence of distinct memory circuits raises
an interesting question. Why would we need two brain circuits for memory
formation versus retrieval? Why not use the same brain circuit for both
functions? When thinking about our memories, we often have experiences that
require memory updating/editing. A common example is a safe neighborhood that
we are familiar with. If we have a traumatic experience in this neighborhood,
our impression is “updated” to a potentially scary neighborhood. Of course, a
similar phenomenon occurs for extremely positive experiences in our lives. We
realized that two, essentially parallel circuits would make it easier and more
efficient to edit/update a memory rather than one single circuit. In a set of
experiments, we were able to find evidence in support of this suggestion,
specifically that as the subiculum recall circuit is activated, simultaneous
activation of the direct hippocampal CA1 to EC layer 5-memory formation circuit
allows us to add new information to the recalled memory.
While rapid memory updating/editing is one
reason to have distinct memory circuits for memory formation versus retrieval,
we expect that future research will discover many other functions. For example,
we found that in the early stages of Alzheimer’s disease, memory retrieval but not formation is
impaired, suggesting that changes in the subiculum brain circuit may contribute
to these symptoms.