In-vitro reproduction of long-lasting effects of stress on memory

In-vitro reproduction of long-lasting effects of stress on memory

Scientists reproduced the same phenomenon as memory consolidation by using organotypic slice cultures of the cerebral cortex and elucidated that stress interfered with memory consolidation.

Humans and animals have innate self-protecting mechanisms for alleviating stress. This is why it was difficult to determine if the results of animal experiments were affected by the stress applied by experimenters or by the effects from animals’ homeostatic response. Therefore, some conflicting results had been reported. However, in the in vitro system, the effects applied by experimenters can be directly examined.

This group had previously found that repeated stimulus to organotypic slice cultures of the cerebral cortex formed new synapses, which is the same phenomenon as the repetition-dependent memory consolidation process, and examined its mechanism.

Naming this structural plasticity RISE (repetitive LTP-induced synaptic enhancement) and assuming it to be a potential in vitro reproduction of repetition-dependent memory consolidation, authors analyzed cellular mechanisms.

In this research, the group elucidated that synapse formation is inhibited by the reproduction of stress known to cause memory defects. When they applied a glucocorticoid (dexamethasone, Dex) to the culture to mimic acute excess stress and demonstrated its blockade of RISE. Since excess stress interferes with behavioral memory consolidation, the parallelism between RISE in vitro and memory consolidation in vivo is supported.

Authors found that the glucocorticoid interfered with RISE by suppressing the increment of dendritic spine fluctuation that precedes a net increase in spine density.
As cultures can be maintained for a long period, it is possible to examine long-term effects. This group’s achievement will be useful for developing therapeutic methods for and preventive measures against stress-induced memory defects.