Imbalanced pattern completion vs. separation in cognitive disease: network simulations of synaptic pathologies predict a personalized therapeutics strategy

Table 2 Example Cross-Therapeutic Predictions for Overall Averages of Disease Populations

Disease or model	Memory rescue observed with	Other predicted targets
Alzheimer's mouse	↓ Inhibition [32–34]	↑ LTP, ↑ connectivity, ↓ LTD
Down synd. mouse
Human Schizophrenia	↑ Inhibition [35, 36]	↓ LTP, ↓ connectivity, ↑ LTD
Angelman mouse
Fragile × mouse	↑ LTP [37–40]	↓ Inhibition, ↓ LTD, ↑ connectivity
Huntington's mouse

The first column lists disease conditions or mouse models where therapeutic rescue of memory has been observed. The second column lists the synaptic property that was targeted or observed to be altered by the treatment (see discussion for details). The third column lists other predicted targets that should function to rebalance memory performance by altering the pattern completion vs. pattern separation bias with the same polarity as the observed effective treatment (see Figure 8). Note that while differential involvement of compensatory mechanism, genetic context, etc., between individuals is expected to result in heterogeneity within a given disease group, that significant improvements were seen on averaged measures of memory function in these studies supports these coarse predictions of therapeutic efficacy within groups. The potential need for personalized assay of completion vs. separation function is illustrated in Figure 9.

ISSN: 1471-2202