Recording from the same neuron with high-density CMOS probes and patch-clamp: a ground-truth dataset and an experiment in collaboration.

Abstract

We built a rig to perform patch-clamp and extracellular recordings from the same neuron in vivo. In this setup, the axes of two micromanipulators are precisely aligned and their relative position tracked in real-time, allowing us to accurately target patch-clamp recordings to neurons near an extracellular probe. We used this setup to generate a publicly-available dataset where a cortical neurons spiking activity is recorded in patch-clamp next to a dense CMOS Neuropixels probe. "Ground-truth" datasets of this kind are rare but valuable to the neuroscience community, as they power the development and improvement of spike-sorting and analysis algorithms, tethering them to empirical observations. In this article, we describe our approach and report exploratory and descriptive analysis on the resulting dataset. We study the detectability of patch-clamp spikes on the extracellular probe, within-unit reliability of spike features and spatiotemporal dynamics of the action potential waveform. We open discussion and collaboration on this dataset through an online repository, with a view to producing follow-up publications. PrologueOur efforts to record from the same neuron in vivo using patch-clamp and dense extracellular probes have resulted in three outputs: a publicly-available dataset (http://bit.ly/paired_recs), a manuscript, and a code repository (http://bit.ly/paired_git). Together, these three components form the publication arising from the experiments we have performed. The role of the dataset is to be downloaded and re-used. The role of the manuscript is to describe the experimental methods through which we acquired the dataset, explain it and showcase which types of questions it can be used to address. The repository has two roles: first, promoting reproducibility and error correction. By making our analysis and figure-generation code freely-available, we wish to make our analysis procedures clear and enable the reader to reproduce our results from the raw data, alerting us to any potential mistakes. Second, the repository will form a living, dynamic and interactive component of the publication: a forum for open collaboration on this dataset. Any interested scientists can contribute to it, joining us in detailed exploration of these recordings with a view to producing follow-up publications in which they will be credited for their input. Why did we opt to publish this way? The first reason is that the very nature of the project we here describe - recording the same neuron with patch-clamp and extracellular probes - invites an open science and open source approach. This is because the primary use of this type of "ground truth" validation data is to aid the development of new sorting and analysis algorithms, as well as to benchmark and improve existing ones. The second reason is that despite being conceptually very simple, this project generated a large and complex dataset that can be tackled in many ways and used to address different types of question. Some of these questions are beyond the reach of our analytical expertise; others lie even beyond the scope of our scientific imagination. By releasing the dataset and providing a repository for scientific discussion and collaboration, we aim to maximise its scientific return to the community. Instead of having each interested research group work in isolation, we hope that by encouraging collaboration and discussion between peers we can foster synergy between them that will lead to work of greater scientific value. Although datasets like ours are exquisitely suited for such an approach, we believe this publication strategy needs to become more widely adopted in neuroscience. We were pleased to note recent publications spontaneously and independently using similar approaches1-4, in what may well be evidence of convergent thinking. Perhaps the time has come for new publication and collaboration paradigms. We will elaborate on this subject during the Epilogue. For now, let us get back to electrophysiological recordings, before we begin an experiment on scientific collaboration.