Simon Schultz

Imperial College London
Session: Building a framework for understanding circuit function session


From photon to pipette: optical and electrophysiological tools for studying intact neural circuits.

Advances in neurotechnology are revolutionising our ability to determine how neural circuit function underpins behavioural phenomena such as perception, memory and action, and how its dysfunction leads to disruption of those behaviours. In particular, optical approaches, in combination with electrophysiology, allow the role of targeted individual circuit elements in behaviour to be studied.

Two-photon targeted whole-cell patch clamp recording now allows genetically targeted cell classes to be electrophysiologically characterised, in head-fixed behaving preparations. However, this technique has a relatively low hit rate, and is difficult to learn, limiting its dissemination. For this reason, we developed a robotically automated two-photon targeted patch clamp recording system (Annecchino et al, 2017). Our system uses closed-loop control based on computer vision using the two photon microscope to iteratively adjust the trajectory of a pipette navigating to a user-selected target, compensating for the effects of pipette-induced brain motion. It has successfully been used to record from inhibitory interneurons, cortical pyramidal cells, cerebellar Purkinje cells, and astrocytes, with performance equivalent to a skilled human operator. To study learning and memory processes, and also changes in neural circuits due to neurodegeneration, it is important to be able to revisit the same cells in a brain over extended time periods for functional recording. We have developed a system to do this optically, in head-fixed mice behaving in a flat, real-world environment (Neurotar). We demonstrate this by showing calcium signals recorded over multiple days from cells in the hippocampus of mice performing a spatial memory task.