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The stereotrode: a new technique for simultaneous isolation of several single units in the central n
... This poses challenges due to both intrinsic noise of the recording system, typically in the low microvolt range [1], and " far-field " noise due to signals from other neurons. The latter can be partially overcome with specialized methods to isolate the signals from individual neurons including careful positioning of fine-tipped electrodes close to individual cells, " triangulation " of neuron signals by recording simultaneously at several nearby points in space [2], and application of algorithms and statistics to separate neurons based on their waveform features [3, 4]. The relationship of the extracellular potential waveform to transmembrane potentials (i.e., membrane currents) has practical implications for sorting multiunit activity and identifying neuronal classes (e.g., bursting cells). ...
... Moreover their composition was such that they were difficult to implant, unless they were bundled together or reinforced. In spite of these apparent disadvantages, in 1983, McNaughton et al. [2] exploited some of these features as a primary advantage through the invention of the stereotrode. The stereotrode consisted of two Teflon-insulated 20 μm (75 % Pt/25 % Ir) wires twisted together and cut transversely with a pair of sharp scissors. ...
... Robinson [59] noted that if an electrode is plated, the impedance will drop, but as time goes by, the impedance will gradually rise and experimenters often have to re-plate the electrodes just prior to use. The early introduction of the stereotrode consisted of a platinum-iridium wires that were plated with platinum to lower their impedance [2]. Soon thereafter, with the introduction of the nichrome tetrode, gold plating was used to reduce impedance [8]. ...
Chapter 1 laid the groundwork for extracellular electrophysiology and the history of microelectrode and microdrive development. However, one of the most technically advanced areas of electrode fabrication is found in the microprobe (e.g., silicon probes) industry where nanoscale fabrication techniques are used to increase recorded neuron yield. To date, these probes have the highest number of contacts per probe and can be combined with integrated circuits, optogenetic control, and drug delivery. This chapter will review a history of development in this field, emphasizing technical advances and what it means for the investigation of neurons.
... This method has been immensely useful for studying neural activity and coding in a wide range of species and neural structures, ranging from single nerve fibers in invertebrate sensory organs [9,10] to cortical neurons involved in cognition, memory, and navigation in awake, behaving animals and humans111213141516171819. However, most such studies so far have used unit recording only for determining spike patterns, firing frequencies, and spike timing [20], so the detailed waveform of each EC spike has normally not been of interest, except spike sorting212223 and sometimes differentiating cell types [24]. Studies of the EC waveform have also not considered the effects of routine filtering [25] or considered cut-off frequencies below 300 Hz [3]. ...
... Second, some high-pass filters will cause overshoots in the signal, thus introducing ''ringing'' in the waveform.Figure 2 shows the effect of applying an order-2 Butterworth high-pass filter or a singlepole (RC) high-pass filter with cut-off frequencies from 12.5 to 800 Hz. An analog version of the order-2 Butterworth filter design with 600 Hz cut-off is often used to isolate single units in extracellular recordings [21,22,24,29,34]. The output signals (blue trace inFigure 2) from cut-off frequencies in the range 200–800 Hz are severely distorted. ...
... The variability in the waveform estimates (mean and standard deviation) with regression and highpass filtering is shown inFigure 7B. Multichannel spike recordings allow spike-sorting based on spike amplitudes, since the latter depend on the distances between the cell and the electrodes [2,22232426]. The peak amplitudes of the high-pass filtered spikes were proportional to the correct spike amplitude, which indicates that they might still be used for spikesorting . ...
Extracellular (EC) recordings of action potentials from the intact brain are embedded in background voltage fluctuations known as the "local field potential" (LFP). In order to use EC spike recordings for studying biophysical properties of neurons, the spike waveforms must be separated from the LFP. Linear low-pass and high-pass filters are usually insufficient to separate spike waveforms from LFP, because they have overlapping frequency bands. Broad-band recordings of LFP and spikes were obtained with a 16-channel laminar electrode array (silicone probe). We developed an algorithm whereby local LFP signals from spike-containing channel were modeled using locally weighted polynomial regression analysis of adjoining channels without spikes. The modeled LFP signal was subtracted from the recording to estimate the embedded spike waveforms. We tested the method both on defined spike waveforms added to LFP recordings, and on in vivo-recorded extracellular spikes from hippocampal CA1 pyramidal cells in anaesthetized mice. We show that the algorithm can correctly extract the spike waveforms embedded in the LFP. In contrast, traditional high-pass filters failed to recover correct spike shapes, albeit produceing smaller standard errors. We found that high-pass RC or 2-pole Butterworth filters with cut-off frequencies below 12.5 Hz, are required to retrieve waveforms comparable to our method. The method was also compared to spike-triggered averages of the broad-band signal, and yielded waveforms with smaller standard errors and less distortion before and after the spike.
... State-of-the-art in vitro HD-MEAs integrate tens of thousands of electrodes and feature spatial resolutions of <20 µm with thousands of peripheral recording amplifiers on a single chip ( Eversmann et al., 2003;Berdondini et al., 2009;Frey et al., 2010;Du et al., 2011;Hierlemann et al., 2011;Huys et al., 2012;Johnson et al., 2013;Ballini et al., 2014;Bertotti et al., 2014;Rossant et al., 2016;Dragas et al., 2017;Tsai et al., 2017). Similarly, for in vivo neural acquisition systems, early devices, such as the stereotrode (McNaughton et al., 1983), tetrode (O' Keefe and Recce, 1993;Gray et al., 1995), and micro-needle probe (Campbell et al., 1991) for recording extracellular field potentials from the intact brain, have yielded way to HD-MEAs of several hundred electrodes microfabricated on a thin silicon shaft (Najafi and Wise, 1986;Blanche, 2005;Wise et al., 2008;Ward et al., 2009;Jun et al., 2017;Mora Lopez et al., 2017), which are now being used in large-scale multi-unit recording systems. ...
... A wide range of electrode sizes has been used for extracellular recording. For in vivo probes, the sizes range from 10 to 125 µm in diameter (Hubel, 1957;McNaughton et al., 1983;Campbell et al., 1991;O'Keefe and Recce, 1993;Blanche, 2005;Ward et al., 2009;Du et al., 2011;Mora Lopez et al., 2017). For in vitro applications, Kim et al. (2014) explored electrode sizes ranging from 5 to 120 µm in diameter. ...
Advances in microfabrication technology have enabled the production of devices containing arrays of thousands of closely spaced recording electrodes, which afford subcellular resolution of electrical signals in neurons and neuronal networks. Rationalizing the electrode size and configuration in such arrays demands consideration of application-specific requirements and inherent features of the electrodes. Tradeoffs among size, spatial density, sensitivity, noise, attenuation, and other factors are inevitable. Although recording extracellular signals from neurons with planar metal electrodes is fairly well established, the effects of the electrode characteristics on the quality and utility of recorded signals, especially for small, densely packed electrodes, have yet to be fully characterized. Here, we present a combined experimental and computational approach to elucidating how electrode size, and size-dependent parameters, such as impedance, baseline noise, and transmission characteristics, influence recorded neuronal signals. Using arrays containing platinum electrodes of different sizes, we experimentally evaluated the electrode performance in the recording of local field potentials (LFPs) and extracellular action potentials (EAPs) from the following cell preparations: acute brain slices, dissociated cell cultures, and organotypic slice cultures. Moreover, we simulated the potential spatial decay of point-current sources to investigate signal averaging using known signal sources. We demonstrated that the noise and signal attenuation depend more on the electrode impedance than on electrode size, per se, especially for electrodes <10 μm in width or diameter to achieve high-spatial-resolution readout. By minimizing electrode impedance of small electrodes (<10 μm) via surface modification, we could maximize the signal-to-noise ratio to electrically visualize the propagation of axonal EAPs and to isolate single-unit spikes. Due to the large amplitude of LFP signals, recording quality was high and nearly independent of electrode size. These findings should be of value in configuring in vitro and in vivo microelectrode arrays for extracellular recordings with high spatial resolution in various applications.
... The simplest way of getting multiple recording sites in an area of interest is by twisting or intertwining insulated micro-wires, thus forming a quite stable bundle (e.g. McNaughton, O`Keefe et al. 1983; Gray, Maldonado et al. 1995; Gritsun, G. Engler et al. 2007). The production process can even be sped up by bundling micro-wires with Poly-Tetra-Fluor- Ethylen (PTFE or Teflon®) shrinking tubes (Mankodiya, Krapohl et al. 2009).Fig. ...
... The production process can even be sped up by bundling micro-wires with Poly-Tetra-Fluor- Ethylen (PTFE or Teflon®) shrinking tubes (Mankodiya, Krapohl et al. 2009).Fig. 2. Microwire bundle electrodes from left: a) stereotrode ((McNaughton, O`Keefe et al. 1983) with permission), b) tetrode (courtesy of T. Davidson, Stanford) and c) Niotrode bundle awaiting finishing process steps (Mankodiya, Krapohl et al. 2009) . ...
The basically electrical nature of the brain's information processing opens a splendid way to learn about its details by using extracellular, microwire recordings to eavesdrop on the activity and information exchange among its neuronal constituents. This method has the advantage over glass micropipettes of bringing quite a sturdy probe into the vicinity of a more or less randomly selected neuron. With this method an immense volume of knowledge was acquired with single - and multiple-electrode recordings from the living brain. This chapter discusses the examples to illustrate that the technology of electrophysiological microrecordings - and for that matter stimulation as well-has come a long way toward multisite and minimally traumatic brain interfacing devices. However, the future of these technologies is even more exciting than the past, since the combination of electrical with optical modalities puts new procedures at the hands of neuroscientists and perhaps even clinical practitioners.
... Neuronal activity recorded from stereotrodes (McNaughton et al., 1983) was amplified (20ϫ) at the head stage (HST/8o50-G20-GR, Plexon, Inc., Dallas, TX) and then passed through a differential preamplifier with a gain of 50 (PBX2/16sp-r-G50, Plexon, Inc.). LFPs were filtered between 0.7-170 Hz (PBX2/16sp-r-G50, Plexon, Inc.). ...
Hippocampal theta oscillations have a temporally asymmetric waveform shape, but it is not known if this theta asymmetry extends to all other cortical regions involved in spatial navigation and memory. Here, using both established and improved cycle-by-cycle analysis methods, we show that theta waveforms in the postrhinal cortex are also temporally asymmetric. On average, the falling phase of postrhinal theta cycles lasts longer than the subsequent rising phase. There are, however, rapid changes in both the instantaneous amplitude and instantaneous temporal asymmetry of postrhinal theta cycles. These rapid changes in amplitude and asymmetry are very poorly correlated, indicative of a mechanistic disconnect between these theta cycle features. We show that the instantaneous amplitude and asymmetry of postrhinal theta cycles differentially encode running speed. Although theta amplitude continues to increase at the fastest running speeds, temporal asymmetry of the theta waveform shape plateaus after medium speeds. Our results suggest that the amplitude and waveform shape of individual postrhinal theta cycles may be governed by partially independent mechanisms and emphasize the importance of employing a single cycle approach to understanding the genesis and behavioral correlates of cortical theta rhythms. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
... Hubei's invention has had far-reaching impact in both neuroscience and neuroengineering. These electrodes enabled seminal contributions to visual neurophysiology with Wiesel 6 , and ushered in the development of newer probes, ranging from tetrodes [G] 7 to microfabricated silicon Michigan-type microelectrode arrays [G] 8 and Utah-type microelectrode arrays [G] 9 (MEAs; Fig. 1). ...
Neural recording electrode technologies have contributed considerably to neuroscience by enabling the extracellular detection of low-frequency local field potential oscillations and high-frequency action potentials of single units. Nevertheless, several long-standing limitations exist, including low multiplexity, deleterious chronic immune responses and long-term recording instability. Driven by initiatives encouraging the generation of novel neurotechnologies and the maturation of technologies to fabricate high-density electronics, novel electrode technologies are emerging. Here, we provide an overview of recently developed neural recording electrode technologies with high spatial integration, long-term stability and multiple functionalities. We describe how these emergent neurotechnologies can approach the ultimate goal of illuminating chronic brain activity with minimal disruption of the neural environment, thereby providing unprecedented opportunities for neuroscience research in the future.
... Moreover, since adjacent cells exhibit action potentials with very similar amplitude and time course, some or all of the action potentials may be lumped together. Stereotrodes which consist of two teflon-insulated platinumiridium alloy microwires twisted together [39], tetrodes which have a bundle of four teflon-insulated platinumiridium alloy microwires [40] were developed to avoid these potential errors in classification. ...
Brain is complex organ composed of numerous glial cells and neurons to convey information using chemical and electrical signals. Neural interface technology using the electrical brain signals has attracted great attention for the clinical and experimental applications. Electrode as the neural interface is the most important part in stimulating neural cells or recording neural activities. In this paper, we provide an overview of electrodes for recording the electrical brain signal. The noninvasive electrodes are primarily used to capture electroencephalogram (EEG) from outside the skull while the implantable electrodes are employed to measure electrocorticogram (ECoG), local field potential (LFP) or spike activity. Recent progress in microfabrication technology enables the development of on-board electrode that combines the entire signal processing including amplification, filtering, and digitization. This will contribute to diagnostic and therapeutic application of the neural interface for restoring physical, psychological and social functions by improving motor, sensory or cognitive abilities.
... DESPITE THE RAPID ADVANCEMENT of brain imaging techniques offering both high spatial and temporal resolution, electrophysiological tools are still widely used methods to investigate the complex spatiotemporal activity patterns of neuronal circuits. 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). ...
Recording simultaneous activity of a large number of neurons in distributed neuronal networks is crucial to understand higher order brain functions. Here, we demonstrate the in vivo performance of a recently developed electrophysiological recording system comprising a two-dimensional, multi-shank, high-density silicon probe with integrated CMOS electronics. The system implements the concept of electronic depth control (EDC), which enables the electronic selection of a limited number of recording sites on each of the probe shafts. This innovative feature of the system permits simultaneous recording of local field potentials (LFP), and single- and multiple-unit activities (SUA and MUA, respectively) from multiple brain sites with high quality and without the actual physical movement of the probe. To evaluate the in vivo recording capabilities of the EDC probe, we recorded LFP, MUA and SUA in acute experiments from cortical and thalamic brain areas of anesthetized rats and mice. The advantages of large-scale recording with the EDC probe are illustrated by investigating the spatiotemporal dynamics of pharmacologically induced thalamocortical slow wave activity in rats, by comparing the firing and burst properties of neurons located in various thalamic nuclei and by the two-dimensional tonotopic mapping of the auditory thalamus. In mice, spatial distribution of thalamic responses to optogenetic stimulation of the neocortex was examined. Utilizing the benefits of the EDC system may result in a higher yield of useful data from a single experiment compared to traditional passive multielectrode arrays, and thus in the reduction of animals needed for a research study.
... Metal wire electrodes have been used for acute recordings since the first half of the XX th century. Several types of multichannel electrodes have been developed, including stereotrodes (McNaughton et al., 1983), multiwire arrays, polymer substrate probes (Rousche et al., 2001; Lind et al., 2013), ceramics-based probes (Moxon et al., 2004) and various types of silicon-substrate probes (Wise et al., 1970; Campbell et al., 1991; Jones et al., 1992; Aarts et al., 2008; Musa et al., 2009; Andrei et al., 2012a; Lopez et al., 2014). Electrodes for chronic use have different mechanical properties, resulting in different degrees of invasiveness to the brain tissue. ...
Neural prostheses have already a long history and yet the cochlear implant remains the only success story about a longterm sensory function restoration. On the other hand, neural implants for deep brain stimulation are gaining acceptance for variety of disorders including Parkinsons disease and obsessive-compulsive disorder. It is anticipated that the progress in the field has been hampered by a combination of technological and biological factors, such as the limited understanding of the longterm behavior of implants, unreliability of devices, biocompatibility of the implants among others. While the field's understanding of the cell biology of interactions at the biotic-abiotic interface has improved, relatively little attention has been paid on the mechanical factors (stress, strain), and hence on the geometry that can modulate it. This focused review summarizes the recent progress in the understanding of the mechanisms of mechanical interaction between the implants and the brain. The review gives an overview of the factors by which the implants interact acutely and chronically with the tissue: blood-brain barrier (BBB) breach, vascular damage, micromotions, diffusion etc. We propose some design constraints to be considered in future studies. Aspects of the chronic cell-implant interaction will be discussed in view of the chronic local inflammation and the ways of modulating it.
... The diameter of each wire that works as an individual signal site is 12.7 lm, and the final braided microelectrode is about 150 lm in diameter. Since the braided electrode consists of 23 wires, it can collect signals from 23 different channels in contact with multiple neurons28293031. One of the critical processes in preparation of the braided microelectrode is to cut the wires perpendicularly after braiding process. ...
Excimer laser ablation is a versatile technique that can be used for a variety of different materials. Excimer laser ablation overcomes limitations of conventional two-dimensional (2D) microfabrication techniques and facilitates three-dimensional (3D) micromanufacturing. Previously, we have reported a characterization study on 248 nm KrF excimer laser micromachining. This paper extends the study to 193 nm ArF excimer laser micromachining on five representative micro-electro-mechanical systems (MEMS) materials (Si, soda-lime glass, SU-8, polydimethylsiloxane (PDMS), and polyimide). Relations between laser parameters (fluence, frequency and number of laser pulses) and etch performances (etch rates, aspect ratio, and surface quality) were investigated. Etch rate per shot was proportional to laser fluence but inversely proportional to number of laser pulses. Laser frequency did not show a notable impact on etch rates. Aspect ratio was also proportional to laser fluence and number of laser pulses but was not affected by laser frequency. Materials absorbance spectrum was found to have important influence on etch rates. Thermal modeling was conducted as well using numerical simulation to investigate how the photothermal ablation mechanism affects the etching results. Thermal properties of material, primarily thermal conductivity, were proved to have significant influence on etching results. Physical deformation in laser machined sites was also investigated using scanning electron microscopy (SEM) imaging. Element composition of redeposited materials around ablation site was analyzed using energy dispersive x-ray spectroscopy (EDXS) analysis. Combined with our previous report on KrF excimer laser micromachining, this comprehensive characterization study provides guidelines to identify optimized laser ablation parameters for desired microscale structures on MEMS materials. In order to demonstrate the 3D microfabrication capability of ArF excimer laser, cutting and local removal of insulation for a novel floating braided neural probe made of polyimide and nichrome was conducted successfully using the optimized laser ablation parameters obtained in the current study.
... The need for close-packed neural recording electrodes arises from the desire to record the activity of a single neuron from multiple points in space, which facilitates the data analysis [1],[2]. Stereotrodes and tetrodes, which contain 2 and 4 tightly twisted wires respectively, are commonly used in neuroscience and provide examples of the value that close-packed recordings can have, even when small-scale: such spatial oversampling helps greatly with the " spike sorting " problem in which recorded electrical events are attributed to individual neurons [3],[4]. Silicon based microelectrodes, developed over the past few decades [5]–[8], have recently been designed to include denser arrays of electrodes than in the past [9]–[11], including active probes with the ability to record a subset of points from a dense array [12]– [15]. ...
Objective:
Neural recording electrodes are important tools for understanding neural codes and brain dynamics. Neural electrodes that are closely packed, such as in tetrodes, enable spatial oversampling of neural activity, which facilitates data analysis. Here we present the design and implementation of close-packed silicon microelectrodes to enable spatially oversampled recording of neural activity in a scalable fashion.
Methods:
Our probes are fabricated in a hybrid lithography process, resulting in a dense array of recording sites connected to submicron dimension wiring.
Results:
We demonstrate an implementation of a probe comprising 1000 electrode pads, each 9 × 9 μm, at a pitch of 11 μm. We introduce design automation and packaging methods that allow us to readily create a large variety of different designs.
Significance:
We perform neural recordings with such probes in the live mammalian brain that illustrate the spatial oversampling potential of closely packed electrode sites.
... However, the measurement of spontaneous nanomolar Ch fluctuations across small heterogeneous regions like hippocampal sub-layers is technically challenging and requires further optimization of the biosensor design. In particular: (a) the size of the recording sites should be small enough to allow resolution of small brain regions like hippocampal sub-layers; (b) enzyme immobilization should be efficient in order to keep good sensitivity at small electrode surfaces; (c) given that in most cortical and dorsal-hippocampal regions the gradient of LFP profiles is much steeper across the dorso-ventral axis, the ChOx and sentinel sites should be located at the same depth in order to optimize common LFP mode rejection using sentinel channel; (d) since complex impedance spectra of ChOx and sentinel sites are, in general, expected to be different across wide range of frequencies, common mode rejection procedure has to be performed in the complex form in the frequency domain, which should improve signal-tonoise ratio compared to conventional sentinel subtraction; and (e) chronic measurement of Ch dynamics across multiple regions and layers in freely moving animals requires flexible and minimally invasive design of the electrode that can be scaled and individually driven to the target location, similar to conventional stereotrode electrodes for extracellular recordings (McNaughton et al., 1983). An additional concern, related to the use of oxidase-based biosensors in vivo is their O 2 dependence. ...
Acetylcholine (ACh) modulates neuronal network activities implicated in cognition, including theta and gamma oscillations but the mechanisms remain poorly understood. Joint measurements of cholinergic activity and neuronal network dynamics with high spatio-temporal resolution are critical to understand ACh neuromodulation. However, current electrochemical biosensors are not optimized to measure nanomolar cholinergic signals across small regions like hippocampal sub-layers. Here, we report a novel oxidase-based electrochemical biosensor that matches these constraints. The approach is based on measurement of H2O2 generated by choline oxidase (ChOx) in the presence of choline (Ch). The microelectrode design consists of a twisted pair of 50µm diameter Pt/Ir wires (sensor and sentinel), which is scalable, provides high spatial resolution and optimizes common mode rejection. Microelectrode coating with ChOx in chitosan cross-linked with benzoquinone is simple, mechanically robust and provides high sensitivity (324±46nAµM(-1)cm(-2)), a limit of detection of 16nM and a t50 response time of 1.4s. Local field potential (LFP)-related currents dominate high-frequency component of electrochemical recordings in vivo. We significantly improved signal-to-noise-ratio compared to traditional sentinel subtraction by a novel frequency domain common mode rejection procedure that accounts for differential phase and amplitude of LFP-related currents on the two channels. We demonstrate measurements of spontaneous nanomolar Ch fluctuations, on top of which micromolar Ch increases occurred during periods of theta activity in anesthetized rats. Measurements were not affected by physiological O2 changes, in agreement with the low biosensor Km for O2 (2.6µM). Design and performance of the novel biosensor opens the way for multisite recordings of spontaneous cholinergic dynamics in behaving animals.
Copyright © 2015. Published by Elsevier B.V.
... Recording with multi-tip electrodes improves the identification of individual neurons compared to standard single-tip electrodes (McNaughton et al. (1983); Recce and O'Keefe (1989)). Under the assumption that the extracellular space is electrically homogeneous, four-tip electrodes (tetrodes) provide the minimal number of recording channels necessary to identify the spatial position of a source based on the relative spike amplitudes on different electrodes. ...
... For example , if two ring neurons of the same type have about the same distance from their somas to the tip of the recording electrode, it may be very dicult to sort the spikes according to from which neuron they originate. The use of two (stereotrode [50]), four (tetrode [24, 33, 77, 90]) or more [9] close-neighbored recording sites allows for improved spike sorting, since the dierent distances from the electrode tips or contacts allow for triangulation . With present recording techniques and clustering methods one can sort out spike trains from tens of neurons from single tetrodes and hundreds of neurons with multishank electrodes [9]. ...
... The recording electrodes consisted of eight bundles of four platinum-iridium wires (90% platinum, 10% iridium; HM-L insulated, 25-m bare wire diameter, California Fine Wire) twisted together. We used electrodes in a tetrode configuration , which allowed clear identification of thalamic units (Gray et al. 1995; McNaughton et al. 1983). Tetrodes were threaded through a 25-gauge guide cannula and protected with a 21-gauge cover. ...
Head-direction cells encode an animal's heading in the horizontal plane. However, it is not clear why the directionality of a cell's mean firing rate differs for clockwise, compared to counter-clockwise head turns (this difference is known as the 'separation angle') in anterior thalamus. Here we investigated, in freely-behaving rats, if intrinsic neuronal firing properties are linked to this phenomenon. We found a positive correlation between the separation angle and the spiking variability of thalamic head-direction cells. To test whether this link is driven by hyperpolarisation-inducing currents, we investigated the effect of thalamic reticular inhibition during high-voltage spindles on directional spiking. While the selective directional firing of thalamic neurons was preserved, we found no evidence for entrainment of thalamic head-direction cells by high-voltage spindle oscillations. We then examined the role of depolarisation-inducing currents in the formation of separation angle. Using a single-compartment Hodgkin-Huxley model, we show that modelled neurons fire with higher frequencies during the ascending phase of sinusoidal current injection (mimicking the head-direction tuning curve), when simulated with higher high-threshold calcium channel conductance. These findings demonstrate that the turn-specific encoding of directional signal strongly depends on the ability of thalamic neurons to fire irregularly in response to sinusoidal excitatory activation. Another crucial factor for inducing phase lead to sinusoidal current injection was the presence of spike-frequency adaptation current in the modelled neurons. Our data support a model in which intrinsic biophysical properties of thalamic neurons mediate the physiological encoding of directional information.
... Such ''reconstructed population codes'' can improve the classification and prediction of stimuli or stimulus responses (Eskandar, Richmond, & Optican, 1992; Gochin, Colombo, Dorfman, Gerstein, & Gross, 1994; Miller, Li, & Desimone, 1993 ). With technical developments over the past decades, simultaneous monitoring of activities of many neurons has become more feasible (Buzsaki, 2004; Harris, Henze, Csicsvari, Hirase, & Buzsaki, 2000; McNaughton, O'Keefe, & Barnes, 1983; Schmidt, 1999). For example, Georgopoulos and his colleagues were among the first to apply a population-vector method to analyze ensemble firing patterns corresponding to arm movements of monkeys (Georgopoulos, Schwartz, & Kettner, 1986). ...
It has been widely recognized that the understanding of the brain code would require large-scale recording and decoding of brain activity patterns. In 2007 with support from Georgia Research Alliance, we have launched the Brain Decoding Project Initiative with the basic idea which is now similarly advocated by BRAIN project or Brain Activity Map proposal. As the planning of the BRAIN project is currently underway, we share our insights and lessons from our efforts in mapping real-time episodic memory traces in the hippocampus of freely behaving mice. We show that appropriate large-scale statistical methods are essential to decipher and measure real-time memory traces and neural dynamics. We also provide an example of how the carefully designed, sometime thinking-outside-the-box, behavioral paradigms can be highly instrumental to the unraveling of memory-coding cell assembly organizing principle in the hippocampus. Our observations to date have led us to conclude that the specific-to-general categorical and combinatorial feature-coding cell assembly mechanism represents an emergent property for enabling the neural networks to generate and organize not only episodic memory, but also semantic knowledge and imagination.
... 4(b)] . The ability to distinguish between action potential shapes originating from different neurons was shown to be improved by assembling individual microwires into tightly wound stereotrodes (two intertwined microwires) and tetrodes (four microwires) [75], [76] [seeFig. 4(c)] . ...
The brain is a large network of interconnected neurons where each cell functions as a nonlinear processing element. Unraveling the mysteries of information processing in the complex networks of the brain requires versatile neurostimulation and imaging techniques. Optogenetics is a new stimulation method which allows the activity of neurons to be modulated by light. For this purpose, the cell-types of interest are genetically targeted to produce light-sensitive proteins. Once these proteins are expressed, neural activity can be controlled by exposing the cells to light of appropriate wavelengths. Optogenetics provides a unique combination of features, including multimodal control over neural function and genetic targeting of specific cell-types. Together, these versatile features combine to a powerful experimental approach, suitable for the study of the circuitry of psychiatric and neurological disorders. The advent of optogenetics was followed by extensive research aimed to produce new lines of light-sensitive proteins and to develop new technologies: for example, to control the distribution of light inside the brain tissue or to combine optogenetics with other modalities including electrophysiology, electrocorticography, nonlinear microscopy, and functional magnetic resonance imaging. In this paper, the authors review some of the recent advances in the field of optogenetics and related technologies and provide their vision for the future of the field.
... In an attempt to characterize local circuit dynamics, combined electrophysiological and imaging techniques have started to map out neocortical circuits (Bock et al., 2011;Ko et al., 2011). With recent developments in multielectrode recording technology, it has also become possible to monitor large numbers of neurons simultaneously with high temporal resolution (McNaughton et al., 1983;Csicsvari et al., 2003;Buzsaki, 2004). Even though this number is still small relative to the total number of neurons, one advantage of ensemble recordings is that it can greatly facilitate the study of spike-train interactions, because the number of neuron pairs increases as the square of the number of units recorded. ...
Characterization of synaptic connectivity is essential to understanding neural circuit dynamics. For extracellularly recorded spike trains, indirect evidence for connectivity can be inferred from short-latency peaks in the correlogram between two neurons. Despite their predominance in cortex, however, significant interactions between excitatory neurons (E) have been hard to detect because of their intrinsic weakness. By taking advantage of long duration recordings, up to 25 h, from rat prefrontal cortex, we found that 7.6% of the recorded pyramidal neurons are connected. This corresponds to ∼70% of the local E-E connection probability that has been reported by paired intracellular recordings (11.6%). This value is significantly higher than previous reports from extracellular recordings, but still a substantial underestimate. Our analysis showed that long recording times and strict significance thresholds are necessary to detect weak connections while avoiding false-positive results, but will likely still leave many excitatory connections undetected. In addition, we found that hyper-reciprocity of connections in prefrontal cortex that was shown previously by paired intracellular recordings was only present in short-distance, but not in long distance (∼300 micrometers or more) interactions. As hyper-reciprocity is restricted to local clusters, it might be a minicolumnar effect. Given the current surge of interest in very high-density neural spike recording (e.g., NIH BRAIN Project) it is of paramount importance that we have statistically reliable methods for estimating connectivity from cross-correlation analysis available. We provide an important step in this direction.
... The second set of recordings is done in vivo on rats. These recordings are obtained by implanting tetrodes or silicon probes which simultaneously record neural activity on several layers of the prefrontal cortex [1]. Probes can be implanted for several weeks in a rat, allowing for the study of mechanisms of memory formation. ...
We describe the selective cluster expansion (SCE) of the entropy, a method for inferring an Ising model which describes the correlated activity of populations of neurons. We re-analyze data obtained from multielectrode recordings performed in vitro on the retina and in vivo on the prefrontal cortex. Recorded population sizes N range from N = 37 to 117 neurons. We compare the SCE method with the simplest mean field methods (corresponding to a Gaussian model) and with regularizations which favor sparse networks (L1 norm) or penalize large couplings (L2 norm). The network of the strongest interactions inferred via mean field methods generally agree with those obtained from SCE. Reconstruction of the sampled moments of the distributions, corresponding to neuron spiking frequencies and pairwise correlations, and the prediction of higher moments including three-cell correlations and multi-neuron firing frequencies, is more difficult than determining the large-scale structure of the interaction network, and, apart from a cortical recording in which the measured correlation indices are small, these goals are achieved with the SCE but not with mean field approaches. We also find differences in the inferred structure of retinal and cortical networks: inferred interactions tend to be more irregular and sparse for cortical data than for retinal data. This result may reflect the structure of the recording. As a consequence, the SCE is more effective for retinal data when expanding the entropy with respect to a mean field reference S − SMF, while expansions of the entropy S alone perform better for cortical data.
... This traditional approach has contributed to the bulk of our understanding of the arousal state of animals, brain rhythms, and functional categorization of neuronal response properties in different brain regions (Buzs á ki, 2006). Also, multielectrode sterotrodes have been employed to triangulate the location of recording neurons (McNaughton et al., 1983). Extracellular recordings have been both acute and long-term. ...
Abstract With increasing use of various techniques to record optically and electrophysiologically from awake behaving animals and the growing developments of brain-machine interfaces, one might wonder if the use of acute-slice physiology is on its deathbed. Have we actually arrived at a stage where we can abandon the use of acute slices, with most of the information about brain functions coming from in vivo experiments? We do not believe that this is the case, given that our understanding of the nuts and bolts of the nervous system, such as ion channels and transporters in near-native state, neuronal compartmentalization, and single-neuron computation, is far from complete. We believe that in the foreseeable future, questions in these fields will still be best addressed by acute-slice physiology. We approach this review from the perspective of improving acute-slice physiology so it can continue to provide relevant and valuable contributions to neuroscience. We conclude that the death of acute-slice physiology is an obituary prematurely written, merely due to waxing and waning trends in science and the shortsightedness of investigators. Acute-slice physiology has at least one more life to live after the hype around new techniques has passed, but it needs to reinvent itself in light of current knowledge.
... Such ''reconstructed population codes'' can improve the classification and prediction of stimuli or stimulus responses (Eskandar, Richmond, & Optican, 1992; Gochin, Colombo, Dorfman, Gerstein, & Gross, 1994; Miller, Li, & Desimone, 1993 ). With technical developments over the past decades, simultaneous monitoring of activities of many neurons has become more feasible (Buzsaki, 2004; Harris, Henze, Csicsvari, Hirase, & Buzsaki, 2000; McNaughton, O'Keefe, & Barnes, 1983; Schmidt, 1999). For example, Georgopoulos and his colleagues were among the first to apply a population-vector method to analyze ensemble firing patterns corresponding to arm movements of monkeys (Georgopoulos, Schwartz, & Kettner, 1986). ...
It has been widely recognized that the understanding of the brain code would require large-scale recording and decoding of brain activity patterns. In 2007 with support from Georgia Research Alliance, we have launched the Brain Decoding Project Initiative with the basic idea which is now similarly advocated by BRAIN project or Brain Activity Map proposal. As the planning of the BRAIN project is currently underway, we share our insights and lessons from our efforts in mapping real-time episodic memory traces in the hippocampus of freely behaving mice. We show that appropriate large-scale statistical methods are essential to decipher and measure real-time memory traces and neural dynamics. We also provide an example of how the carefully designed, sometime thinking-outside-the-box, behavioral paradigms can be highly instrumental to the unraveling of memory-coding cell assembly organizing principle in the hippocampus. Our observations to date have led us to conclude that the specific-to-general categorical and combinatorial feature-coding cell assembly mechanism represents an emergent property for enabling the neural networks to generate and organize not only episodic memory, but also semantic knowledge and imagination.
... The spatial distribution of action potentials recorded on multiple detectors contains more information than simple coincidence. For example, McNaughton et al. (1983) simultaneously recorded action potentials from several neurons on two closely spaced electrodes. Spike trains were then separated based on the ratio of their heights on the two electrodes. ...
Independent component analysis (ICA) was used to separate action potential trains recorded with voltage-sensitive dyes in the isolated brain preparation of the seaslug Tritonia. It was assumed that the membrane potential of each neuron was an approximately independent source and that detectors (photodiodes) recorded linear mixtures of sources. These assumptions appear to be reasonable as ICA outperformed existing methods for separating spike trains in optical recording data. Spike trains, artifacts, and noise were assigned to different output channels (independent components). The ICA analysis method was also less labor intensive than other methods.
... A central constraint on data collection in chronic electrophysiology is the difficulty of recording the activity of identified, individual neurons (termed " units " ). While the use of tetrodes (Wilson and McNaughton, 1993; Gray et al., 1995; Jog et al., 2002; Nguyen et al., 2009) or stereotrodes (McNaughton et al., 1983 ) have made it possible to reliably identify individual neurons in recordings and to record from the same neurons over consecutive sessions (Tolias et al., 2007), obtaining sufficiently clear data from large numbers of electrodes remains a challenge. The presented drive design addresses this constraint by enabling highly parallel recordings in mice without sacrificing the ability to precisely reposition many individual electrodes. ...
Electrophysiological recordings from ensembles of neurons in behaving mice are a central tool in the study of neural circuits. Despite the widespread use of chronic electrophysiology, the precise positioning of recording electrodes required for high-quality recordings remains a challenge, especially in behaving mice. The complexity of available drive mechanisms, combined with restrictions on implant weight tolerated by mice, limits current methods to recordings from no more than 4-8 electrodes in a single target area. We developed a highly miniaturized yet simple drive design that can be used to independently position 16 electrodes with up to 64 channels in a package that weighs ~2 g. This advance over current designs is achieved by a novel spring-based drive mechanism that reduces implant weight and complexity. The device is easy to build and accommodates arbitrary spatial arrangements of electrodes. Multiple optical fibers can be integrated into the recording array and independently manipulated in depth. Thus, our novel design enables precise optogenetic control and highly parallel chronic recordings of identified single neurons throughout neural circuits in mice.
... The use of multiple close-by recording sites-stereotrodes (Mc-Naughton, Okeefe, & Barnes, 1983), tetrodes (Okeefe & Recce, 1993;Gray, Maldonado, Wilson, & McNaughton, 1995), or more recently, high-density multielectrode arrays (Segev, Goodhouse, Puchalla, & Berry, 2004;Blanche, Spacek, Hetke, & Swindale, 2005;Frey, Egert, Heer, Hafizovic, & Hierlemann, 2009;Lambacher et al., 2011)-has been proposed to increase the number of identified neurons. The basic idea of these electrodes is to improve spike sorting by observing the neurons from different locations, given that spike shapes that are hard to differentiate in a given channel can be separated by considering their differences in other channels. ...
We present a novel method to generate realistic simulations of extracellular recordings. The simulations were obtained by superimposing the activity of neurons placed randomly in a cube of brain tissue. Detailed models of individual neurons were used to reproduce the extracellular action potentials of close-by neurons; to reduce the computational load, the contributions of neurons further away were simulated using previously recorded spikes with their amplitude normalized by the distance to the recording electrode. To make the simulations more realistic, we also considered a model of a finite-size electrode by averaging the potential along the electrode surface and modeling the electrode-tissue interface with a capacitive filter. This model allowed studying the effect of the electrode diameter on the quality of the recordings and how it affects the number of identified neurons after spike sorting. Given that not all neurons are active at a time, we also generated simulations with different ratios of active neurons and estimated the ratio that matches the signal-to-noise values observed in real data. Finally, we used the model to simulate tetrode recordings.
... See Supplemental Experimental Procedures for details. Electrophysiology Neuronal activity recorded from stereotrodes (McNaughton et al., 1983) was multiplied by 20 with an operational amplifier at the head stage (HST/8o50- G20-GR, Plexon, Inc., Dallas, TX). Signals were then passed through a differential preamplifier with a gain of 50 (PBX2/16sp-r-G50, Plexon, Inc.). ...
Postrhinal cortex, rodent homolog of the primate parahippocampal cortex, processes spatial and contextual information. Our hypothesis of postrhinal function is that it serves to encode context, in part, by forming representations that link objects to places. To test this hypothesis, we recorded postrhinal neurons and local field potentials (LFPs) in rats trained on a two-choice, visual discrimination task. As predicted, many postrhinal neurons signaled object-location conjunctions. Another large proportion encoded egocentric motor responses. In addition, postrhinal LFPs exhibited strong oscillatory rhythms in the theta band, and many postrhinal neurons were phase locked to theta. Although correlated with running speed, theta power was lower than predicted by speed alone immediately before and after choice. However, theta power was significantly increased following incorrect decisions, suggesting a role in signaling error. These findings provide evidence that postrhinal cortex encodes representations that link objects to places and suggest postrhinal theta modulation extends to cognitive as well as spatial functions.
... To test this hypothesis, we first had to establish that visual and mechanical sensory information reaches the CC. Because of the size of these structures (the combined EB and FB are ∼400 µm × 200 µm in Blaberus discoidalis), we chose to address this very basic question with an extracellular multi-channel recording technique (McNaughton et al., 1983; Ritzmann et al., 2008). This technique has proven to be very useful, in that it allows us to record from numerous neurons simultaneously for long periods of time. ...
Animals must routinely deal with barriers as they move through their natural environment. These challenges require directed changes in leg movements and posture performed in the context of ever changing internal and external conditions. In particular, cockroaches use a combination of tactile and visual information to evaluate objects in their path in order to effectively guide their movements in complex terrain. When encountering a large block, the insect uses its antennae to evaluate the object’s height then rears upward accordingly before climbing. A shelf presents a choice between climbing and tunneling that depends on how the antennae strike the shelf; tapping from above yields climbing, while tapping from below causes tunneling. However, ambient light conditions detected by the ocelli can bias that decision. Similarly, in a T-maze turning is determined by antennal contact but influenced by visual cues. These multi-sensory behaviors led us to look at the central complex as a center for sensori-motor integration within the insect brain. Visual and antennal tactile cues are processed within the central complex and, in tethered preparations, several central complex units changed firing rates in tandem with or prior to altered step frequency or turning, while stimulation through the implanted electrodes evoked these same behavioral changes. To further test for a central complex role in these decisions, we examined behavioral effects of brain lesions. Electrolytic lesions in restricted regions of the central complex generated site specific behavioral deficits. Similar changes were also found in reversible effects of procaine injections in the brain. Finally, we are examining these kinds of decisions made in a large arena that more closely matches the conditions under which cockroaches forage. Overall, our studies suggest that CC circuits may indeed influence the descending commands associated with navigational decisions, thereby making them more context dependent.
... Striatal lesions impair the procedural learning but not declarative learning forms of the task [164,165]. Electrophysiological recordings within the basal ganglia and hippocampus during declarative and procedural learning tasks have confirmed the central and specific involvement of these regions in learning and memory [166][167][168]. ...
Core psychoanalytic constructs may be impossible to study directly using neuroscience and imaging methodologies. Nevertheless, experimental paradigms have been developed and are being applied that are at least relevant to understanding the neural bases of certain core theoretical constructs within psychoanalysis. These paradigms have demonstrated the likely contributions of: (1) the nucleus accumbens and related limbic circuitry in assigning valence within the pleasure/unpleasure continuum of affective experience; (2) the reticular formation, thalamus, amygdala, and cortex within arousal circuits in assigning personal salience to those affective experiences; (3) frontostriatal systems in subserving top-down processing in the CNS, which in turn contributes to numerous important psychological functions, including the control of drives and the construction of experience according to preestablished conceptual schemas—processes that likely underlie cognitive distortions, projection, and transference phenomena; and (4) multiple memory systems, particularly the procedural learning systems based within the dorsal striatum and declarative learning systems in the mesial temporal lobe, that likely contribute to memories within the domain of the descriptive unconscious, and the interactions across affective and cognitive memory systems, that might contribute to memory formations within the dynamic unconscious. q 2005 Association for Research in Nervous and Mental Disease. Published by Elsevier B.V. All rights reserved.
... Thus, improved methods are needed for the simultaneous recording of closely spaced neuronal populations with minimal damage to the hard wiring of the brain network. The recent advent of localized multisite extracellular recording techniques has dramatically increased the yield of isolated neurons (Gray et al., 1995; McNaughton et al., 1983; Wilson and McNaughton, 1993). With only one recording site, signals from many neurons with similar size and orientation and which are at the same distance from the tip will provide the same magnitude signal, making single-cell isolation difficult. ...
In order to understand the involvement of activity of single neurons in the context of the activity generated in small or
larger neuronal networks, electrophysiological methods and morphological techniques need to be combined. In this chapter I
describe a combination of methods designed to enable researchers to record the electrophysiological activity of single neurons
in the intact brain, to analyze the interactions of these identified neurons with the surrounding neuronal network, and to
investigate afterward the neuroanatomical characteristics of the recorded neurons.
High-yield electrophysiological extracellular recording in freely moving rodents provides a unique window into the temporal dynamics of neural circuits. Recording from unrestrained animals is critical to investigate brain activity during natural behaviors. The use and implantation of high-channel-count silicon probes represent the largest cost and experimental complexity associated with such recordings making a recoverable and reusable system desirable. To address this, we have designed and tested a novel 3D printed head-gear system for freely moving mice and rats. The system consists of a recoverable microdrive printed in stainless steel and a plastic head cap system, allowing researchers to reuse the silicon probes with ease, decreasing the effective cost, and the experimental effort and complexity. The cap designs are modular and provide structural protection and electrical shielding to the implanted hardware and electronics. We provide detailed procedural instructions allowing researchers to adapt and flexibly modify the head-gear system.
An important requisite for understanding brain function is the identification of behavior and cell activity correlates. Silicon probes are advanced electrodes for large-scale electrophysiological recording of neuronal activity, but the procedures for their chronic implantation are still underdeveloped. The activity of hippocampal place cells is known to correlate with an animal's position in the environment, but the underlying mechanisms are still unclear. To investigate place cells, here we describe a set of techniques which range from the fabrication of devices for chronic silicon probe implants to the monitoring of place field activity in a cue-enriched treadmill apparatus. A micro-drive and a hat are built by fitting and fastening together 3D-printed plastic parts. A silicon probe is mounted on the micro-drive, cleaned, and coated with dye. A first surgery is performed to fix the hat on the skull of a mouse. Small landmarks are fabricated and attached to the belt of a treadmill. The mouse is trained to run head-fixed on the treadmill. A second surgery is performed to implant the silicon probe in the hippocampus, following which broadband electrophysiological signals are recorded. Finally, the silicon probe is recovered and cleaned for reuse. The analysis of place cell activity in the treadmill reveals a diversity of place field mechanisms, outlining the benefit of the approach.
Developments in microfabrication technology have enabled the production of neural electrode arrays with hundreds of closely spaced recording sites, and electrodes with thousands of sites are under development. These probes in principle allow the simultaneous recording of very large numbers of neurons. However, use of this technology requires the development of techniques for decoding the spike times of the recorded neurons from the raw data captured from the probes. Here we present a set of tools to solve this problem, implemented in a suite of practical, user-friendly, open-source software. We validate these methods on data from the cortex, hippocampus and thalamus of rat, mouse, macaque and marmoset, demonstrating error rates as low as 5%.
Continuous neural spiking records were obtained from the mesothoracic ganglion of the dragonfly. For analysis the 12 s records of all 58 discriminated cells were "tracked" across three continuous behavioral states: pre-flight, flight and post-flight. The recorded spike amplitudes and angles (widths) for each cell were used to construct a simple map of individual cell positions relative to each other within the ganglion. Individual cell activity patterns were then characterized both with respect to neighboring cell locations and patterns of cell spiking observed across three behavioral states. The results indicated that this technique for constructing a "neighboring cell map" effectively reflects the known histological features of the ganglionic cell architecture. The gross firing histories of individual cells were found to correspond to the overall spike patterns of neighboring ganglionic cells as opposed to more distal cells. Such relationships suggest that the physical layout of this ganglionic network may help to determine or bias individual cell firing histories that occur during different behavioral states in the dragonfly.
To develop neuroprostheses that will provide the nervous system with artificial sensory input through the sensory nerves to which they will be connected, on one hand we have to determine how external stimuli are represented, coded and transmitted by the Nervous System, how neurons and neuronal ensembles process, encode and transmit perceptual information. On the other we need to know how the central nervous system reacts to the implanted neuroprostheses and quantify its anatomic and functional alterations due to the artificial input it receives from our devices. Here we present mathematical and electrophysiological methods for signal acquisition, analysis, and information coding in the tactile sensory system that include a wavelet and principal component analysis-based method for neural signal analysis and different types of frequency-based signal processing and coding performed simultaneously by the sensory neurons. Finally we present a quantitative morphological study of the effects of the neuroprosthetic stimulation using a stereological approach.
When recording action potentials (spikes) from many neurons simultaneously via multichannel microelectrodes the overlapping of spikes from different neurons is a demanding problem for detection and classification of spikes (spike sorting). Since multichannel electrodes provide better possibilities to separate the superimposed waveforms, we refined an algorithm for separation of overlapping spikes for the use on multichannel recordings and tested it on simulated data with different numbers of signal channels and with several signal parameters.We show that the larger the number of signal channels the better the separation that may be achieved, especially under demanding recording conditions.
Electrophysiological recording of neuronal action potentials from behaving animals requires portable, precise and reliable devices for positioning of multiple microelectrodes in the brain. We propose a semi-automatic microdrive system for independent positioning of up to 8 electrodes (or tetrodes) in a rat (or larger animals). Device is intended to be used in chronic long term recording applications with freely moving animals. In such applications micro drives are used to move the electrodes vertically to achieve the best quality of a signal from isolated brain cells. Our design is based on independent stepper motors with lead screws which will offer single steps of ~10 µm semi-automatically controlled from the computer. . Micro-drive system prototype for 1 electrode was developed and tested. For experimental evaluation of proposed solution, magnetic linear and rotary encoders that provide information about electrode displacement and motor shaft movement were designed. Because of the lack of the systematic test procedures dedicated to such applications, we propose the evaluation method similar to ISO norm for industrial robots. Repeatability, accuracy and backlash of the drive are estimated basing on results from measurements. According to the given assumptions and preliminary tests, the device should provide greater repeatability and positioning accuracy than hand-controlled manipulators, that are available on the market. Automatic positioning will also shorten the course of the experiment and improve the acquisition of signals from nerve cells. Presented solution is a prototype. Before the final micro drive system will be constructed, we plan to carry out experimental trials of the device during recording of electrophysiological signals in acute experiments.
Significance
Organizing large, multidimensional datasets by subgrouping data as clusters is a major challenge in many fields, including neuroscience, in which the spike activity of large numbers of neurons is recorded simultaneously. We present a mathematical approach for clustering such multidimensional datasets in a relatively high-dimensional space using as a prototype datasets characterized by high background spike activity. Our method incorporates features allowing reliable clustering in the presence of such strong background activity and, to deal with large size of datasets, incorporates automated implementation of clustering. Our approach effectively identifies individual neurons in spike data recorded with multiple tetrodes, and opens the way to use this method in other domains in which clustering of complex datasets is needed.
Due to the high spatial selectivity and resolution with high accessibility to single neurons, penetrating neural electrodes have been used for neuronal recording or stimulation in specific applications although they are invasive, thus inducing more inflammatory response and damages to the tissue, compared to non-penetrating electrodes. Penetrating electrodes are mainly made up of stiff materials such as metal wires, silicon, or glass. Compared to microwire electrodes, siliconbased penetrating electrodes are fabricated in precise designs and dimensions, often in forms of array with higher number of independent channels. Although precise 2-D and 3-D electrode structures are used in many applications, efforts to make them more biocompatible and long-lasting have been reported recently. On the other hand, soft materials such as polymers have also been lately used in penetrating electrodes to accommodate their flexibility and mechanical properties that are more favorable to neural tissues, minimizing adverse effects on tissues. Polymer-based electrodes are promising for future applications where better biocompatibility is required although technical hurdles in using them in long term have to be overcome.
Brain function depends on simultaneous electrical, chemical and mechanical signaling at the cellular level. This multiplicity has confounded efforts to simultaneously measure or modulate these diverse signals in vivo. Here we present fiber probes that allow for simultaneous optical stimulation, neural recording and drug delivery in behaving mice with high resolution. These fibers are fabricated from polymers by means of a thermal drawing process that allows for the integration of multiple materials and interrogation modalities into neural probes. Mechanical, electrical, optical and microfluidic measurements revealed high flexibility and functionality of the probes under bending deformation. Long-term in vivo recordings, optogenetic stimulation, drug perturbation and analysis of tissue response confirmed that our probes can form stable brain-machine interfaces for at least 2 months. We expect that our multifunctional fibers will permit more detailed manipulation and analysis of neural circuits deep in the brain of behaving animals than achievable before.
The brain is composed of many different types of neurons. Therefore, analysis of brain activity with single-cell resolution could provide fundamental insights into brain mechanisms. However, the electrical signal of an individual neuron is very small, and precise isolation of single neuronal activity from moving subjects is still challenging. To measure single-unit signals in actively behaving states, establishment of technologies that enable fine control of electrode positioning and strict spike sorting is essential. To further apply such a single-cell recording approach to small brain areas in naturally behaving animals in large spaces or during social interaction, we developed a compact wireless recording system with a motorized microdrive. Wireless control of electrode placement facilitates the exploration of single neuronal activity without affecting animal behaviors. Because the system is equipped with a newly developed data-encoding program, the recorded data are readily compressed almost to theoretical limits and securely transmitted to a host computer. Brain activity can thereby be stably monitored in real time and further analyzed using online or offline spike sorting. Our wireless recording approach using a precision motorized microdrive will become a powerful tool for studying brain mechanisms underlying natural or social behaviors.
Availability of the instantaneous velocity of a legged robot is usually required for its efficient control. However, estimation of velocity only on the basis of robot kinematics has a significant drawback: the robot is not in touch the ground all of the time, or its feet may twist. In this paper we introduce a method for velocity and tilt estimation in a walking robot. This method combines a kinematic model of the supporting leg and readouts from an inertial sensor. It can be used in any terrain, regardless of the robot’s body design or the control strategy applied, and it is robust in regards to foot twist. It is also immune to limited foot slide and temporary lack of foot contact.
While the subject of learning has attracted immense interest from both behavioral and neural scientists, only relatively few investigators have observed single-neuron activity while animals are acquiring an operantly conditioned response, or when that response is extinguished. But even in these cases, observation periods usually encompass only a single stage of learning, i.e. acquisition or extinction, but not both (exceptions include protocols employing reversal learning; see Bingman et al.(1) for an example). However, acquisition and extinction entail different learning mechanisms and are therefore expected to be accompanied by different types and/or loci of neural plasticity. Accordingly, we developed a behavioral paradigm which institutes three stages of learning in a single behavioral session and which is well suited for the simultaneous recording of single neurons' action potentials. Animals are trained on a single-interval forced choice task which requires mapping each of two possible choice responses to the presentation of different novel visual stimuli (acquisition). After having reached a predefined performance criterion, one of the two choice responses is no longer reinforced (extinction). Following a certain decrement in performance level, correct responses are reinforced again (reacquisition). By using a new set of stimuli in every session, animals can undergo the acquisition-extinction-reacquisition process repeatedly. Because all three stages of learning occur in a single behavioral session, the paradigm is ideal for the simultaneous observation of the spiking output of multiple single neurons. We use pigeons as model systems, but the task can easily be adapted to any other species capable of conditioned discrimination learning.
Abstract In this article, we evaluated the electrophysiological performance of a novel, high-complexity silicon probe array. This brain-implantable probe implements a dynamically reconfigurable voltage-recording device, coordinating large numbers of electronically switchable recording sites, referred to as electronic depth control (EDC). Our results show the potential of the EDC devices to record good-quality local field potentials, and single- and multiple-unit activities in cortical regions during pharmacologically induced cortical slow wave activity in an animal model.
The BRAIN project recently announced by the president Obama is the reflection of unrelenting human quest for cracking the brain code, the patterns of neuronal activity that define who we are and what we are. While the Brain Activity Mapping proposal has rightly emphasized on the need to develop new technologies for measuring every spike from every neuron, it might be helpful to consider both the theoretical and experimental aspects that would accelerate our search for the organizing principles of the brain code. Here we share several insights and lessons from the similar proposal, namely, Brain Decoding Project that we initiated since 2007. We provide a specific example in our initial mapping of real-time memory traces from one part of the memory circuit, namely, the CA1 region of the mouse hippocampus. We show how innovative behavioral tasks and appropriate mathematical analyses of large datasets can play equally, if not more, important roles in uncovering the specific-to-general feature-coding cell assembly mechanism by which episodic memory, semantic knowledge, and imagination are generated and organized. Our own experiences suggest that the bottleneck of the Brain Project is not only at merely developing additional new technologies, but also the lack of efficient avenues to disseminate cutting edge platforms and decoding expertise to neuroscience community. Therefore, we propose that in order to harness unique insights and extensive knowledge from various investigators working in diverse neuroscience subfields, ranging from perception and emotion to memory and social behaviors, the BRAIN project should create a set of International and National Brain Decoding Centers at which cutting-edge recording technologies and expertise on analyzing large datasets analyses can be made readily available to the entire community of neuroscientists who can apply and schedule to perform cutting-edge research.
Understanding the principles that underlie information processing by neuronal networks requires simultaneous recordings from large populations of well isolated single units. Twisted wire tetrodes (TWTs), typically made by winding together four ultrathin wires (diameter-12 to 25 microns), are ideally suited for such population recordings. They are advantageous over single electrodes; both with respect to quality of isolation as well as the number of single units isolated and have therefore been used extensively for superficial cortical recordings. However, their limited tensile strength poses a difficulty to their use for recordings in deep brain areas. We therefore developed a method to overcome this limitation and utilize tetrodes for electrophysiological recordings in the inferotemporal cortex of rhesus macaque. We fabricated a novel, stiff tetrode called the tube tetrode (TuTe) and developed a multi-tetrode driving system for advancing up to 5 TuTes through a ball and socket chamber to precise locations in the temporal lobe of a rhesus macaque. The signal quality acquired with TuTes was comparable to conventional TWTs and allowed excellent isolation of multiple single units. We describe here a simple method for constructing TuTes, which requires only standard laboratory equipment. Further, our TuTes can be easily adapted to work with other microdrives commonly used for electrophysiological investigation in the macaque brain and produce minimal damage to the cortex along its path because of their ultrathin diameter. The tetrode development described here could allow studying neuronal populations in deep lying brain structures previously difficult to reach with the current technology.
Spatial navigation and the firing of hippocampal place cells can be driven as much by what an animal knows about its spatial world as by what it immediately experiences at a given location. Results of an experiment with 2 experienced rats show that place fields are disrupted in a familiar room in darkness if the animal is not shown its starting location but remain intact in darkness if the starting location is known to the animal. A minimal computational model proposes that conditional associations between places and movements are established during learning about an environment. The model suggests how compound movement/place representations could be combined with hippocampal spatial representations to account for the "blind" navigation phenomena. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
The perirhinal cortex (PRC) is known to play an important role in object recognition. Little is known, however, regarding the activity of PRC neurons during the presentation of stimuli that are commonly used for recognition memory tasks in rodents, that is, three-dimensional objects. Rats in the present study were exposed to three-dimensional objects while they traversed a circular track for food reward. Under some behavioral conditions, the track contained novel objects, familiar objects, or no objects. Approximately 38% of PRC neurons demonstrated "object fields" (a selective increase in firing at the location of one or more objects). Although the rats spent more time exploring the objects when they were novel compared to familiar, indicating successful recognition memory, the proportion of object fields and the firing rates of PRC neurons were not affected by the rats' previous experience with the objects. Together, these data indicate that the activity of PRC cells is powerfully affected by the presence of objects while animals navigate through an environment; but under these conditions, the firing patterns are not altered by the relative novelty of objects during successful object recognition. © 2012 Wiley Periodicals, Inc.
The present work describes a new technique for the identification of functional connectivity between neural firing patterns. The simultaneous singleunit recordings obtained from over 50 individual cells in the dragonfly mesothoracic ganglion during three consecutive behavioral states: pre-flight, flight and postflight were evaluated. Each individual spike train was converted into a synthesized analog gradient designed to capture crucial physiological characteristics of the cell from which the spike train emanated. Estimates of network functional connectivity were calculated using correlations between analog gradient spike trains for all possible cell pairings. Both functional excitation and inhibition could be detected in the correlations. The detection of functional connectivity was relatively independent of cell firing rate. More detailed analyses indicated the existence of cellular firing histories and connectivity patterns during flight that strongly resembled the characteristics of a bi-stable oscillator. Such an oscillator, hypothetically, could drive the elevator and depressor motor neuron firing paterns that support wing kinematics. There was no evidence for the functional existence of such an oscillator within either preor post-flight spike records. The detected spatiotemporal patterns of neural activity are hypothesized to be consistent with neural command sequences that the dragonfly might use to control flight. The demonstrated capability to define short-time scale functional relationships between spike trains obtained from dragonfly ganglia should have valuable applications to the comparative study of neural information processing strategies in a variety of other neural systems.
We examined the behavioral modulation of head-directional information processing in neurons of the rat posterior cortices, including the medial prestriate (area Oc2M) and retrosplenial cortex (areas RSA and RSG). Single neurons were recorded in freely moving rats which were trained to perform a spatial working memory task on a radial-arm maze in a cue-controlled room. A dual-light-emitting diode (dual-LED) recording headstage, mounted on the animals' heads, was used to track head position and orientation. Planar modes of motion, such as turns, straight motion, and nonlocomotive states, were categorized using an objective scheme based upon the differential contributions of movement parameters, including linear and angular velocity of the head. Of 662 neurons recorded from the posterior cortices, 41 head-direction (HD) cells were identified based on the criterion of maintained directional bias in the absence of visual cues or in the dark. HD cells constituted 7 of 257 (2.7%) cells recorded in Oc2M, 26 of 311 (8.4%) cells in RSA, and 8 of 94 (8.5%) cells in RSG. Spatial tuning of HD cell firing was modulated by the animal's behaviors in some neurons. The behavioral modulation occurred either at the preferred direction or at all directions. Moreover, the behavioral selectivity was more robust for turns than straight motions, suggesting that the angular movements may significantly contribute to the head-directional processing. These behaviorally selective HD cells were observed most frequently in Oc2M (4/7, 57%), as only 5 of 26 (19%) of RSA cells and none of the RSG cells showed behavioral modulation. These data, taken together with the anatomical evidence for a cascade of projections from Oc2M to RSA and thence to RSG, suggest that there may be a simple association between movement and head-directionality that serves to transform the egocentric movement representation in the neocortex into an allocentric directional representation in the periallocortex.
The patterns of ensemble activity in the hippocampal formation during wakeful, attentive behavior are recapitulated during subsequent resting states. This replay of activity has also been found in several brain regions across many species, indicating a very general biological phenomenon. Concomitantly, transcription of immediate-early genes (IEGs) such as Arc also reoccurs in the same hippocampal neurons, suggesting that IEGs contribute to "off-line" consolidation. If continued IEG expression during rest reflects a correlate of ensemble replay, then the same generality should be observed in IEG transcription patterns. This hypothesis was tested by examining Arc in F344 rats engaging in spatial exploration alongside a rest episode. The probability that an individual neuron participates in "constitutive" Arc expression during rest is increased by recent experience in multiple cortical regions as well as across the septal and temporal poles of the hippocampus, consistent with memory trace reactivation. That is, neurons that were recently active during spatial exploration are preferentially recruited into further Arc expression during subsequent rest. The continued Arc expression, however, occurs in only a small fraction of the cells that were engaged in transcription during previous behavior. This fraction is greatest in CA3 and progressively decreases in CA1, superficial, and deep cortical layers and is consistent with the idea that consolidation occurs rapidly in the hippocampus (centering on the CA3 recurrent network) while changes are much more gradual in neocortical synaptic networks.
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