Work in animal models indicates that presynaptic proteins are markers for changes in synaptic function related to behavior and to medication treatments. Many of these studies examine individual proteins. Relationships between behavior or treatments and multiple, interacting proteins remain less clear. These possibilities are open for analysis, using combinations of transgenic animals, simultaneous assessment of families of proteins, and considering the interactions of genetic variation, environmental stressors, and medications. Research with human samples presents additional challenges in translating molecular findings into clinical implications. Careful assessment of genetic variants may yield insights, provided the consequences of such variants can be assayed directly in experimental systems. Prospective studies of cognition in subjects agreeing to participation in post mortem research may provide a link with animal studies. The availability of high-throughput strategies to assay multiple proteins in multiple brain regions will also provide a rich source of data for modeling the relationships between synaptic function, behavior, and illness. With such a foundation in place, truly novel therapeutic strategies may be developed.

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