Memories Take A Detour In The Brain

Memories are formed in and retrieved from different parts of the brain, according to an optogenetic study by researchers in Japan.

AsianScientist (Aug. 24, 2017) – Scientists in Japan have found that a poorly-understood region of the brain known as the subiculum is critical for memory retrieval. Their findings have been published in Cell.

Memory formation in mammals appears to loop around the hippocampus, mirroring its physical structure: neural signaling from the entorhinal cortex (EC) proceeds through the central hippocampus to an area called CA1. From there, signals either take a ‘direct flight’ to deep EC, or they first make a ‘stopover’ at a region called the subiculum, and then proceed to the EC or other brain regions. The precise function of the subiculum in memory formation and recall remains unclear.

In this study, a research group led by Professor Susumu Tonegawa investigated the role of the subiculum in mouse memory by genetically expressing fluorescent proteins only in these particular neurons. They could then selectively turn them on or off with optogenetics—targeted bursts of light that can activate tagged brain cells.

While ‘turning off’ the subiculum during training had no effect on later recall, mice that had already learned to associate an environment with foot shocks no longer froze when the subiculum cells were silenced during subsequent recall tests. This indicated that the mice could no longer retrieve the memory, and that the subiculum is necessary for retrieval, but not formation, of memories.

Activating the subiculum during the memory test also affected memory recall, in this case seeming to enhance the fearful memory and causing mice to freeze more often. This newly discovered function contrasts with the direct connection from CA1 to deep layers of the EC, which is essential for memory formation, but not retrieval.

Manipulating the subiculum also changed stress hormone levels related to the recall of fear memories. Inhibition of subiculum output to the hypothalamic mammillary bodies stopped corticosterone spiking in the blood in response to fear, but only during memory retrieval, not when footshocks were experienced during training. Conversely, hormone levels increased if this same connection was optogenetically activated, but again, only during memory recall.

“Recall through the subiculum detour may allow memories that are important for triggering instinctual behaviors to be rapidly updated,” said Dr. Dheeraj Roy of the RIKEN-MIT Center.

Although the two hippocampal pathways are largely subserved by the same neurons, only inhibition of the subiculum circuit before testing affected memory recall in the mice. Coordinated fear behaviors like freezing and increases in blood stress hormones may prepare animals to effectively encounter and respond to dangers in their environment.

“The subiculum is unique in that it has a bidirectional effect on memory recall, enhancing recall when activated and impairing recall when inhibited,” said Tonegawa, Director of the RIKEN-MIT Center.

The fact that the subiculum sends outputs to many cortical and subcortical brain regions, and that it is widely believed to be one of the earliest areas affected in Alzheimer’s Disease, makes it an exciting target for memory research.

The article can be found at: Roy et al. (2017) Distinct Neural Circuits for the Formation and Retrieval of Episodic Memories.


Source: RIKEN; Photo: Shutterstock.
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