The sliding threshold of modification hypothesis: application to the effect of hypothyroidism or chronic psychosocial stress and nicotine on synaptic plasticity.

The Bienenstock, Cooper, and Munro (BCM) theory or the sliding threshold model can be used to explain the changes in synaptic plasticity related to learning and memory, namely long-term potentiation (LTP) and depression (LTD). In this study, we applied synaptic plasticity changes induced by either chronic psychosocial stress or hypothyroidism, and their restoration by chronic nicotine treatment, to the sliding threshold model. Psychosocial stress- or hypothyroidism-induced changes in synaptic plasticity generated a shift in the sliding threshold of modification (theta(m)) toward LTD. In addition, chronic nicotine treatment restored the theta(m) to the normal position by normalizing psychosocial stress- or hypothyroidism-induced impairment of LTP and enhancement of LTD. The data correlate with our previous findings: a shift in the balance of kinase/phosphatase toward phosphatase during psychosocial stress or hypothyroidism, which is restored by chronic nicotine treatment.