Simon Schultz, Imperial College London | From photon to pipette: targeted interrogation of cortical circuit function

Abstract

The advent of multiphoton microscopy, in conjunction with an expanding toolkit of fluorescent reporters that can be selectively expressed in defined cell types, has resulted in substantial advances in the development of techniques for studying cortical circuits. In this talk I will describe two approaches. In the first, we use two photon microscopy to target robotically automated whole-cell patch clamp electrophysiology to genetically targeted cell types (Annecchino et al, 2017). A challenge faced in directing a micropipette towards a specific targeted cell in a live brain is that movement of the pipette through brain tissue results in viscoelastic deformation of the tissue, and movement of the target. We solved this problem by means of a computer vision algorithm operating on frames collected in the vicinity of the target, feeding in to a closed-loop trajectory control system. The resulting robotic 2P-targeted electrophysiology system performs as well as an experienced human operator.

In the second part of the talk, I will describe ongoing work aimed at characterising the activity of neural ensembles in the hippocampus, in awake mice performing a spatial exploration task, while head-fixed in a flat, real-world environment. We are able to routinely record the activity of identified neurons over many days. Current work involves application of this approach to characterise changes in memory circuits due to neurodegenerative disease in a number of mouse models of Alzheimer’s Disease.

Literature

• Annecchino, L.A., Morris, A.R., Copeland, C.S., Agabi, O.E., Chadderton, P. and Schultz, S.R., 2017. Robotic Automation of In Vivo Two-Photon Targeted Whole-Cell Patch-Clamp Electrophysiology. Neuron, 95(5), pp.1048-1055. (Link)

SIMON SCHULTZ, Department of Bioengineering | Imperial College London