Novel approaches for interrogating and manipulating synaptic function, structure and plasticity

Synapses throughout the central nervous system are sculpted by neural activity through changes in their size, shape and molecular composition, which either strengthen or weaken communication between neurons. This “plasticity” in synapse function is widely viewed as the central mechanism for information storage in the brain. While many forms of synaptic plasticity have been discovered and their molecular mechanisms intensely investigated, in many cases there is surprisingly little direct evidence linking them to the cognitive functions they are proposed to control. This has remained a challenge due to a lack of tools for rapidly and locally switching on or off the requisite biochemistry and cell biology underlying different plasticity mechanisms in real time, in vivo. We are developing new tools that fill this void with the long- term goal of addressing fundamental gaps in our knowledge concerning how synapses are modified at the molecular level through development and plasticity, how these modifications influence synapse/circuit function and ultimately the relevance of these mechanisms for important cognitive functions like learning and memory.