Exploring scalable computationally informed approaches for in vitro neuronal electrophysiology

Neuronal networks of human-derived neurons represent an emerging opportunity to accelerate research on brain function and neurological disease states. Electrophysiological signals recorded from neuronal networks provide distinctive information on the nature of the network and can be employed to unravel mechanisms of relevant neurodegenerative diseases. The complex architecture of excitatory and inhibitory connections thereby governs the selectivity of neuronal responses that can be observed from the network. Hence, a key step in uncovering the functional connectivity within these networks resides in the accurate analysis of how a single neuron can modulate the circuit function and behavior.

Imec's high-density microelectrode array (HD-MEA) platform is a powerful tool to study these cellular networks at single cell level. The MEA chips can interrogate and interact with the neuronal network grown on top of the sub-cellular sized electrodes by recording their electrical signatures or stimulating them. With more than 16k electrodes and an electrode pitch of 15 mm, the chip provides an unprecedented resolution for neuronal interfacing. Inferring knowledge about developing neural circuits is however not only determined by the scale of data acquisition. Scaling data dimensionality can overwhelm data analysis capacity and lead to exponentially increasing computation times. The implementation of innovative algorithms and experimental paradigms will be required to ensure an increasing rate of scientific discovery while increasing the scale of data.

In this PhD project you will explore algorithmic approaches based on forward biophysical modeling and machine learning and develop a computationally scalable data processing pipeline for data-efficient interrogation of neuronal circuits on the HD-MEA platform. Adaptive selection of recording electrodes will be combined with closed loop experimental feedback to maximize the rate at which electrical profiles can be derived from single neuron and neuronal network behavior. Novel experimental paradigms will be explored to infer network connectivity patterns that are based on external stimulation with different modalities (e.g. mild voltage stimulation or optogenetics). For this interdisciplinary project, you should have a background in neuroscience, biomedical engineering, data science or related fields. Experience in electrophysiology would be desirable. You will be supervised and supported by a team of data/computer scientists, engineers and biologists at imec, in collaboration with neuronal communication experts at VIB and Stanford university.