Multiplexed, High Density Electrophysiology with Nanofabricated Neural Probes

Abstract

Extracellular electrode arrays can reveal the neuronal network correlates of behavior with single-cell, single-spike, and sub-millisecond resolution. However, implantable electrodes are inherently invasive, and efforts to scale up the number and density of recording sites must compromise on device size in order to connect the electrodes. Here, we report on silicon-based neural probes employing nanofabricated, high-density electrical leads. Furthermore, we address the challenge of reading out multichannel data with an application-specific integrated circuit (ASIC) performing signal amplification, band-pass filtering, and multiplexing functions. We demonstrate high spatial resolution extracellular measurements with a fully integrated, low noise 64-channel system weighing just 330 mg. The on-chip multiplexers make possible recordings with substantially fewer external wires than the number of input channels. By combining nanofabricated probes with ASICs we have implemented a system for performing large-scale, high-density electrophysiology in small, freely behaving animals that is both minimally invasive and highly scalable.

Large-scale, high-density (up to 512 channels) recording of local circuits in behaving animals

“…Yet, monitoring a statistically representative fraction of neurons of the investigated circuits in behaving animals is a prerequisite for understanding neuronal computation (Alivisatos et al 2012(Alivisatos et al , 2013Buzsáki 2004;Carandini 2012;Nicolelis et al 1997). Currently, recordings of individual neurons and local field potentials (LFPs) in local circuits at high temporal resolution are possible with wire or nanomachined microelectrodes ("silicon probes"; Blanche et al 2005;Buzsáki 2004;Buzsáki et al 2012;Du et al 2011;Logothetis 2003;Wilson and McNaughton 1993). High-density probes can record from multiple cortical and subcortical structures in the freely behaving animal at the spatial resolution of single neurons (Blanche et al 2005;Buzsáki 2004;Csicsvari et al 2003;Du et al 2011;Fujisawa et al 2008;Montgomery et al 2008).…”

“…Currently, recordings of individual neurons and local field potentials (LFPs) in local circuits at high temporal resolution are possible with wire or nanomachined microelectrodes ("silicon probes"; Blanche et al 2005;Buzsáki 2004;Buzsáki et al 2012;Du et al 2011;Logothetis 2003;Wilson and McNaughton 1993). High-density probes can record from multiple cortical and subcortical structures in the freely behaving animal at the spatial resolution of single neurons (Blanche et al 2005;Buzsáki 2004;Csicsvari et al 2003;Du et al 2011;Fujisawa et al 2008;Montgomery et al 2008). Furthermore, silicon probe recordings can be combined with optogenetic methods for the identification of neuron types and selective manipulation of local circuits (Anikeeva et al 2012;Boyden et al 2005;Royer et al 2010;Stark et al 2012).…”

“…Whereas silicon probe technology is poised to offer everlarger site numbers and smaller volume probes (Du et al 2009(Du et al , 2011, significant improvements and miniaturization are needed at the level of headstage interconnects, signal multiplexing, ultraflexible connection between the animal and the recording equipment, and signal processing (Du et al 2011;Szuts et al 2011;Vandecasteele et al 2012). One critical aspect of miniaturization is the deployment of signal multiplexers.…”

Large-scale recording of thalamocortical circuits: in vivo electrophysiology with the two-dimensional electronic depth control silicon probe

“…Over the past few decades, single-wire electrodes used for in vivo extracellular recording of action potentials evolved into multielectrode arrays covering the range of up to 1,000 recording sites (Bai and Wise 2001;Berényi et al 2014;Blanche et al 2005;Bragin et al 2000;Campbell et al 1991;Chen et al 2009;Cheung 2007;Csicsvari et al 2003;Drake et al 1988;Du et al 2009Du et al , 2011Grand et al 2011;Karmos et al 1982;Khodagholy et al 2015;Kipke et al 2008;Kubie 1984;Lopez et al 2014;Márton et al 2015;McNaughton et al 1983;Michon et al 2016;Okeefe and Recce 1993;Ruther et al 2010;Ruther and Paul 2015;Scholvin et al 2016;Seidl et al 2011Seidl et al , 2012Shobe et al 2015;Torfs et al 2011;Wilson and McNaughton 1993;Wise et al 1970Wise et al , 2008. With such a high number of recording sites neuroscientists are able to monitor the activity of hundreds of neurons simultaneously both in anesthetized and in freely moving animals (Berényi et al 2014;Ifft et al 2013;Nicolelis et al 2003;Vandecasteele et al 2012), which is fundamental for the understanding of complex neuronal computations and higher order cognitive functions, such as learning, memory, or language (Buzsáki 2004).…”

A Neural Probe With Up to 966 Electrodes and Up to 384 Configurable Channels in 0.13 $\mu$m SOI CMOS

“…Two different kinds of signals can be identified in a frequency band of 10 kHz: the local-field potentials (LFPs) in the low frequency range (< 1 kHz) and the action potentials (APs) in the high frequency range (~0. [3][4][5][6][7][8][9][10]. Neural signals present a ~1/f frequency dependency [13], which means that the signals above 10 kHz are highly attenuated.…”