High-density extracellular probes reveal dendritic backpropagation and facilitate neuron classification.

Xiaoxuan Jia,Shawn R Olsen,Samuel D Gale,Christof Koch,Joshua H Siegle,Daniel J Denman,Corbett Bennett

doi:10.1152/jn.00680.2018

Abstract

Different neuron types serve distinct roles in neural processing. Extracellular electrical recordings are extensively used to study brain function but are typically blind to cell identity. Morphoelectrical properties of neurons measured on spatially dense electrode arrays have the potential to distinguish neuron types. We used high-density silicon probes to record from cortical and subcortical regions of the mouse brain. Extracellular waveforms of each neuron were detected across many channels and showed distinct spatiotemporal profiles among brain regions. Classification of neurons by brain region was improved with multichannel compared with single-channel waveforms. In visual cortex, unsupervised clustering identified the canonical regular-spiking (RS) and fast-spiking (FS) classes but also indicated a subclass of RS units with unidirectional backpropagating action potentials (BAPs). Moreover, BAPs were observed in many hippocampal RS cells. Overall, waveform analysis of spikes from high-density probes aids neuron identification and can reveal dendritic backpropagation. NEW & NOTEWORTHY It is challenging to identify neuron types with extracellular electrophysiology in vivo. We show that spatiotemporal action potentials measured on high-density electrode arrays can capture cell type-specific morphoelectrical properties, allowing classification of neurons across brain structures and within the cortex. Moreover, backpropagating action potentials are reliably detected in vivo from subpopulations of cortical and hippocampal neurons. Together, these results enhance the utility of dense extracellular electrophysiology for cell-type interrogation of brain network function.

Highlights

Brain networks are composed of diverse cell types with distinct roles in neural dynamics and processing
The action potential waveforms analyzed in this report refer to the mean waveform for each sorted unit, which is calculated by taking a bootstrapped average from all spikes aligned by their trough
We measured extracellular action potentials from single units with Neuropixels probes, whose dense recording site arrangement allows detection of extracellular waveforms on multiple probe sites. We found that both 1-channel features, such as waveform duration, and multichannel features, such as propagation profile, were useful for classifying neurons

Summary

Introduction

Brain networks are composed of diverse cell types with distinct roles in neural dynamics and processing. In the neocortex, excitatory pyramidal neurons provide local recurrent processing and send long-range projections for information propagation (Harris and Shepherd 2015; Spruston 2008), whereas inhibitory neurons perform gain modulation, control spike timing and rhythms, and shape receptive field. Neuronal cell types are defined by various properties including gene expression, morphology, physiology, and connectivity (Baden et al 2016; Gouwens et al 2018; Harris and Shepherd 2015; Kim et al 2017; Markram et al 2004; Tasic et al 2016; Zeng and Sanes 2017). Optotagging can link extracellular spike measurements to cell types by directly photo-stimulating cells that express a light-sensitive opsin under genetic control (Cohen et al 2012; Kvitsiani et al 2013; Lima et al 2009), but this is largely restricted to transgenic systems and usually only labels one cell population per experiment

Methods

Results

Conclusion