NeuroExaminer - a microfluidic device for physiology-based neural circuit analysis

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Psychiatric disorders affect a large number of the worldwide population. Not surprisingly, prescriptions of neuromodulatory drugs for young children and juveniles, but also adults are constantly rising, in particular in the developed western countries. The implications of these drugs on the physiology of the entire brain, including brain compartments and circuits that are not the primary target of therapeutic intervention, however, are barely understood and suitable diagnostic approaches for humans are unlikely in the near and medium-term future. However, analogous drug characterization studies in brains of other vertebrates, such as the Zerafish, will be informative due to the high evolutionary conservation of the brain circuitry. In the proposed research we will develop a novel device to reveal the physiological consequences of neuromodulatory drug administration regimes on the whole brain in vivo. The core is a miniature device – termed NeuroExaminer – established by advanced methods of microfabrication that allows for precise chemical stimulations and can be combined with whole brain light-sheet microscopy with cellular resolution at the subsecond time-scale. Typically used materials for microfluidics, such as PDMS, however exhibit not only a relatively high auto fluorescence that leads to noise in the imaging, but also the tendency to absorb chemical components, resulting in largely undefined stimuli concentrations. The NeuroExaminer will thus contain microchannels made from glass or from combinations of glass with two photon polymerized elements for precisely controlled compound application with subsecond resolution and steep concentration gradient formation. This will enable to reveal the pharmacokinetics and neuromodulatory functions of any water-soluble compound. In the course of the project we will develop a proof of concept by using the NeuroExaminer to investigate brain-wide alterations induced by two different psychostimulants through continuously monitoring neuronal activity at cellular resolution over at least one hour. This will demonstrate that the NeuroExaminer is a powerful novel instrument to reveal the specific neural activity of drugs, including their lag time until neuromodulation is achieved together with circuit activation or repression in a time-dependent manner. Moreover, our work will provide a much needed method to reveal fundamental insights into neural circuits and allow to test any water soluble compound for a possible neuromodulatory effect. Therefore, basic research in neuroscience, pharmaceutical research for drug development and validation as well as public authorities for evaluating drug safety will profit from the NeuroExaminer. Ultimately, the access to novel neurophysiological diagnostics provided by the NeuroExaminer will help to contribute to novel and better treatments of neuropsychiatric disorders.