In vitro neuronal networks with defined topology enable investigations into how ensemble network geometries and connectivity affect brain activity. These measurements are not possible in vivo due to the complexity of neuronal processes that cannot be measured sufficiently with current technologies. We have developed strategies to grow neuronal circuits with both structurally and functionally directional connections between neurons using polymeric guidance microstructures on multi-electrode arrays (MEAs). While in vitro MEA recordings of extracellular potentials from spiking neurons is standard practice, simultaneous monitoring of neurochemical signaling has not been possible. Recently, rationally designed oligonucleotide sequences termed aptamers demonstrated specific and selective neurotransmitter recognition in physiological environments. Upon target binding, aptamers undergo conformational changes resulting in the rearrangement of the negatively charged backbone at surfaces. Using this technology, we have developed two new systems for parallel monitoring of neurochemical flux and electrophysiology. In the first approach, we functionalize gold MEAs with aptamers hypothesizing target binding will reversibly alter the surface potential, which can be measured as transient changes in voltage. The second approach is to couple aptamers to the inner surface of quartz nanopipettes (~10 nm tip size) to approach patterned neuronal networks from above. Aptamer conformational changes reversibly gate the diffusion of ions between open and closed states under applied bias potential, resulting in measurable changes in ionic current. Such aptamer-functionalized systems will enable sensing of neurotransmitter flux in localized regions of neuronal networks providing potential insight into the mechanisms underpinning synaptic plasticity.

Aptamer-functionalized microelectrodes and nanopipettes to sense neurotransmitters in neuronal networks

2019 Fall National Meeting

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