Studying synaptic plasticity in the human brain and opportunities for drug discovery

Synaptic plasticity is the ability of synaptic connections between neurons to be strengthened or weakened; a process that is central to the information processing within the brain and which plays a particularly important role in enabling higher cognitive processes [1 and 2]. Its role in disease is becoming increasingly clear across a wide spectrum of CNS disorders. Thus, for example, dysfunctional synaptic plasticity has been reported in neurodegenerative disorders such as Alzheimer's Disease (AD) as well as in schizophrenia and in a range of disorders associated with learning disabilities [3]. Moreover, maladaptive plasticity processes in response to specific external challenges are believed to underlie disorders such as addiction and post-traumatic stress disorder (PTSD). The molecular basis of normal and disease plasticity is rapidly being unravelled such that synaptic plasticity now provides a unique platform from which to launch the hunt for highly innovative drugs to treat CNS disease by either, firstly, rectifying identifiable abnormalities in these processes, or secondly, utilizing these processes as a vehicle to rectify, or bypass, other mechanisms underlying disease. In this respect, recent advances have been made in studying synaptic plasticity in humans at the molecular through to clinical level and these approaches now provide a real opportunity to test synaptic plasticity as a treatment paradigm for a wide variety of CNS disorders.

► Numerous preclinical technologies have enabled the dissection of the molecular mechanisms of synaptic plasticity. ► Synaptic plasticity is a fundamental property of the brain when dysfunctional is central to disease. ► Brain imaging and brain stimulation methods can be used to probe plasticity in the human brain. ► Cortical excitability can be measured using various TMS methods. ► Functional plasticity in specific brain areas or brain networks can be measured using fMRI.