Mismatch novelty exploration training enhances hippocampal synaptic plasticity: A tool for cognitive stimulation?

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Memory formation relies on experience-dependent changes in synaptic strength such as long-term potentiation (LTP) or long-term depression (LTD) of synaptic activity, that in turn depend on previous learning experiences through metaplasticity. Novelty detection is a particularly important cognitive stimulus in this respect, and mismatch novelty has been associated with the activation of the hippocampal CA1 area in human studies. A single exposure to a new location of known objects in a familiar environment, a behavioural mismatch novelty paradigm, is known to favour the expression of LTD in hippocampal CA3 to CA1 synaptic transmission in vivo, through short-term metaplasticity. Aiming to shape hippocampal responsiveness to synaptic plasticity phenomena we developed a training program based on exploration of a known environment containing familiar objects, everyday presented in a new location. Repeated exposure to this new location of objects for two weeks caused a mild long-lasting decrease in synaptic efficacy. Furthermore, it enhanced both LTP evoked by theta-burst stimulation and depotentiation evoked by low-frequency stimulation of CA3 to CA1 hippocampal synaptic transmission in juvenile rats. This suggests that training programs using these behavioural tasks involving mismatch novelty can be used to reshape brain circuits and promote cognitive recovery in pathologies where LTP/LTD imbalance occurs, such as epilepsy, aging or Down’s syndrome, an approach that requires further investigation at the behavioural level.

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