Figure 8

Personalized Therapeutics Based on Assay of Network Imbalance. A) The origins of pathological changes in the synaptic phenotypes of LTP, LTD, inhibition, and connectivity are indicated. In addition to direct effects of disease-linked mutations (Table 1), and other genetic or environmental factors, effects of feedback due to developmental or age-related changes, as well as homeostatic compensatory mechanisms, are indicated. B) The key prediction of the simulations is that the summed impact of any constellation of synaptic pathologies will be to imbalance network performance in one of two directions, 1) Separation bias, where despite very low pattern separation error, intolerable errors in pattern completion underlie memory impairment, or 2) Completion bias, where despite very low completion error, intolerable errors in pattern separation underlie memory impairment. C) The proposed approach of using assays of network imbalance to prescribe therapeutic targets is illustrated. Manipulations of each of the synaptic properties predicted to have therapeutic benefits are listed for each type of network imbalance (large arrows). The dashed box is to emphasize that the approach of predicting therapeutics based on assay of network imbalance is agnostic to the underlying synaptic phenotypes and their causes.