Cellular studies in neuroscience are hampered by the fact that in vitro cultures of primary neurons are complex, variable and heterogeneous, making studies on cultured neurons time consuming, labor-intensive and not scalable. Especially for single cell studies on synaptic transmission and cellular trafficking, this is a major limitation. Both in academia and industry, mitotic cells are commonly used as a proxy for neurons (e.g. PC12 cells). However, while being less variable and better scalable, such cells model neurons only to a limited extent. These cells make no functional contacts (synapses) and do not have the same polarized organization that neurons have, limiting studies on synaptic transmission and cellular trafficking. Most commonly prescribed drugs for brain disorders target synapses. Yet, major endeavors to find new therapeutics, e.g. drug screening, lead finding/optimization and safety studies, build either on cells that make no synapses or on labor-intense low-throughput assays. Hence, new, standardized, scalable assays using real (synaptic) neurons, will provide a substantial step forward both for academia and industry.
We established a new approach to electrically record synaptic transmission in many single neurons in parallel, with high-resolution, using nano-electrodes on a chip. We showed that we can grow nerve cells in a regular grid, forming dense networks on a silicon chip. Furthermore, we developed nano-scale versions of the conventional patch clamp electrodes for synaptic recordings on a chip and novel approaches to obtain high resistance seals to the cell membrane. Massive parallel electrical recording with single cell resolution will not only facilitate and standardize cellular assays using real, synaptic neurons, but also upscale throughput, probably by at least 100 fold, which will make synaptic transmission accessible for applications in the pharmaceutical industry and personalized medicine.
