Synaptic plasticity and mental health: methods, challenges and opportunities

Activity-dependent synaptic plasticity is a ubiquitous property of the nervous system that allows neurons to communicate and change their connections as a function of past experiences. Through reweighting of synaptic strengths, the nervous system can remodel itself, giving rise to durable memories that create the biological basis for mental function. In healthy individuals, synaptic plasticity undergoes characteristic developmental and aging trajectories. Dysfunctional plasticity, in turn, underlies a wide spectrum of neuropsychiatric disorders including depression, schizophrenia, addiction, and posttraumatic stress disorder. From a mechanistic standpoint, synaptic plasticity spans the gamut of spatial and temporal scales, from microseconds to the lifespan, from microns to the entire nervous system. With the numbers and strengths of synapses changing on such wide scales, there is an important need to develop measurement techniques with complimentary sensitivities and a growing number of approaches are now being harnessed for this purpose. Through hemodynamic measures, structural and tracer imaging, and noninvasive neuromodulation, it is possible to image structural and functional changes that underlie synaptic plasticity and associated behavioral learning. Here we review the mechanisms of neural plasticity and the historical and future trends in techniques that allow imaging of synaptic changes that accompany psychiatric disorders, highlighting emerging therapeutics and the challenges and opportunities accompanying this burgeoning area of study.