Wednesday, 4 October 2017: 11:40
National Harbor 11 (Gaylord National Resort and Convention Center)
Efforts to understand how neurons within networks interact to control behavior will be greatly facilitated by means with which to measure multiple neuroactive molecules in the brain simultaneously and in near-real time. We are developing an implantable microprobe capable of simultaneous rapid monitoring of three ubiquitous neurotransmitters/neuromodulators: dopamine (DA), glutamate (Glut), and acetylcholine. A detailed mathematical model is guiding electroenzymatic sensor optimization, and the use of a nanostructured Pt deposit has led to improved microsensors for choline and DA operated in constant potential amperometry mode. The creation of microsensor arrays for combined sensing of multiple neurochemicals is facilitated by the use of microcontact printing to deposit specific enzymes on selected microelectrode sites with fine control. Further, we are harnessing the power of optogenetics by incorporating an optical waveguide into our microprobes with microelectrode sensor arrays. This is achieved using an innovative silica-based microprobe design with embedded waveguides and a novel output grating coupler for directional illumination from the center of each neurochemical sensing site. The resultant microprobe enables local modulation of genetically isolated neuron terminals with measurement of transmitter release from those terminals. Our evaluation of probe performance in vivo has focused on the striatum and the basolateral amygdala (BLA). Optically evoked glutamate release has been observed successfully in the BLA of rats, but not in those genetically modified animals whose pre-synaptic activity is subjected to inhibition. Also, the improved DA sensors have enabled detection of electrical stimulation-evoked DA response in the rat dorsal striatum in the drug-naïve state. Further work to correlate multiple transmitter release events with behavioral actions will provide valuable information pertinent to the search for therapeutic interventions for multiple neurological and psychiatric disorders.