Optical control of pain

• A photoswitch named QAQ (pronounced "quack") acts as a light-sensitive local anesthetic.
• QAQ in the trans state blocks many voltage-gated channels and silences neuronal activity. Light converts the photoswitch to cis, reawakening activity.
• QAQ is membrane-impermeant and only affects ion channels when present on the cytoplasmic side of the membrane. One way to achieve this is by injecting QAQ through a patch electrode.
• QAQ can enter into cells through large-pore ion channels, including the heat-sensitive capsaicin receptor (TRPV1) and a receptor for ATP (the P2X receptor), both of which are expressed in pain-sensing neurons.
• In vivo experiments show that QAQ modulates behavioral responses to noxious stimuli in a light-dependent manner.
• Ongoing studies with QAQ show that nociceptive neurons can signal to one another, especially after peripheral nerve injury.

Optical control of dendritic spikes

• Understanding how dendritic spikes affects synaptic integration and plasticity has been hindered by the small fiber diameter and spatial complexity of dendritic trees.
• We use QAQ, DENAQ, and other photoswitches to globally or locally control dendritic excitability.
• By injecting a photoswich into a neuron and projecting a small pattern of light, we can optically regulate voltage-gated channels in subcellular regions.
• Photoswitches provide a way to explore excitability in part of neurons that are inaccessible to direct electrophysiological analysis.