Low throughput screening in neuroscience: using light to study central synapses one at a time.

Neurophotonic approaches have fostered substantial progress in our understanding of the brain by providing an assortment of means to either monitor or manipulate neural processes. Among these approaches, the development of two-photon uncaging provides a useful and flexible approach to manipulate the activity of individual synapses. In this short piece, we explore how this technique has emerged at the intersection of chemistry, optics, and electrophysiology to enable spatially and temporally precise photoactivation for studying functional aspects of synaptic transmission and dendritic integration. We discuss advantages and limitations of this approach, focusing on our efforts to study several functional aspects of glutamate receptors using uncaging of glutamate. Among other advancements, this approach has contributed to further our understanding of the subcellular regulation, trafficking, and biophysical features of glutamate receptors (e.g., desensitization and silent synapse regulation), the dynamics of spine calcium, and the integrative features of dendrites, and how these functions are altered by several forms of plasticity.