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Background Neural responses to electrical stimulation provide valuable information to probe and study the network function. Especially, recording neural responses from the stimulated site provides improved neural interfacing method. However, it is difficult to measure short-delayed responses at the stimulated electrode due to the saturation of the amplifier after stimulation which is called “stimulus artifact”. Despite the advances in handling stimulation artifacts, it is still very challenging to deal with the artifacts if one tries to stimulate and record from the same electrode. New method In this paper, we developed a system consisting of 24 bit ADC and low gain DC-amplifier which allows us to record the entire responses including saturation-free stimulus artifact and neural responses with excellent resolution. Results Our approach showed saturation-free recording after stimulation, which makes it possible to recover neural spike as early as in 2 ms at the stimulating electrode with digital elimination methods. Comparison with Existing methods With our system we could record neural signals after stimulation that was difficult with high gain and high pass filtered recording system due to amplifier saturation. Conclusions Our new system can enhance interface performance with its higher robustness and with simple system configuration.

BACKGROUND: Independent-components-analysis (ICA) successfully separated electrically-evoked compound action potentials (ECAPs) from the stimulation artefact and noise (ECAP-ICA, Akhoun et al., 2013). NEW METHOD: This paper shows how to automate the ECAP-ICA artefact cancellation process. Raw-ECAPs without artefact rejection were consecutively recorded for each stimulation condition from at least 8 intra-cochlear electrodes. Firstly, amplifier-saturated recordings were discarded, and the data from different stimulus conditions (different current-levels) were concatenated temporally. The key aspect of the automation procedure was the sequential deductive source categorisation after ICA was applied with a restriction to 4 sources. The stereotypical aspect of the 4 sources enables their automatic classification as two artefact components, a noise and the sought ECAP based on theoretical and empirical considerations. RESULTS: The automatic procedure was tested using 8 cochlear implant (CI) users and one to four stimulus electrodes. The artefact and noise sources were successively identified and discarded, leaving the ECAP as the remaining source. The automated ECAP-ICA procedure successfully extracted the correct ECAPs compared to standard clinical forward masking paradigm in 22 out of 26 cases. COMPARISON WITH EXISTING METHOD(S): ECAP-ICA does not require extracting the ECAP from a combination of distinct buffers as it is the case with regular methods. It is an alternative that does not have the possible bias of traditional artefact rejections such as alternate-polarity or forward-masking paradigms. CONCLUSIONS: The ECAP-ICA procedure bears clinical relevance, for example as the artefact rejection sub-module of automated ECAP-threshold detection techniques, which are common features of CI clinical fitting software.

Background Active amplification electrodes are becoming more popular for ERP data collection, as they amplify the EEG at the scalp and thereby potentially decrease the influence of ambient electrical noise. However, the performance of active electrodes has not been directly compared with that of passive electrodes in the context of collecting ERPs from a cognitive task. Here, the performance of active and passive amplification electrodes in the same digitizing amplifier system was examined. Method In Experiment 1, interelectrode impedance in an electrically quiet setting was manipulated to determine whether, in such recording conditions, active electrodes can outperform passive ones. In Experiment 2, the performance of active electrodes at the limits of natural skin impedance was explored, as was the relationship between active amplification circuitry and voltage stability in averaged EOG. Results Results reveal a complex pattern of interrelations between electrode type, impedance, and voltage stability, indicating that which type of electrode is “best” depends non-trivially on the circumstances in which data are being collected. Comparison with existing methods Traditional, passive electrodes acquired the cleanest data observed in any of the acquisition conditions at very low impedance, but not at any impedance >2 kΩ. Conclusion Active electrodes perform better than passive ones at all impedances other than very low ones; however, this is qualified by the additional finding that during fast voltage fluctuations, such as those most desirable in most ERP studies, active electrodes are less able to accurately follow the EEG than passive ones.

We present the first, fully-integrated, two-channel implementation of a patch-clamp measurement system. With this “PatchChip” two simultaneous whole-cell recordings can be obtained with rms noise of 8 pA in a 10 kHz bandwidth. The capacitance and series-resistance of the electrode can be compensated up to 10 pF and 100 MΩ respectively under computer control. Recordings of hERG and Nav 1.7 currents demonstrate the system's capabilities, which are on par with large, commercial patch-clamp instrumentation. By reducing patch-clamp amplifiers to a millimeter size micro-chip, this work paves the way to the realization of massively-parallel, high-throughput patch-clamp systems for drug screening and ion-channel research. The PatchChip is implemented in a 0.5 μm silicon-on-sapphire process; its size is 3 × 3 mm2 and the power consumption is 5 mW per channel with a 3.3 V power supply.

Custom made multi-channel headstage preamplifiers are traditionally powered by battery. By the use of an isolated unregulated DC/DC converter integrated circuit (DCP010512B from Texas Instruments Inc., TX, USA), here we describe the implementation of a galvanically isolated low-noise power supply board for multi-channel headstage preamplifiers. The implemented galvanically isolated power supply board provides the same quality noise free recording as the battery power supply. The non-isolated part of the power supply board is powered by standard 230 V AC/6 V DC wall mount adapter or USB cable. The described galvanically isolated power supply board can replace the batteries in preamplifier power supplies without any deterioration of the quality of recordings.

Brain-computer interfaces (BCIs) based on steady-state visual evoked potentials (SSVEPs) have been investigated increasingly in the last years. This type of brain signals resulting from repetitive flicker stimulation has the same fundamental frequency as the stimulation including higher harmonics. This study investigated how the classification accuracy of a 4-class BCI system can be improved by localizing individual electroencephalogram (EEG) recording positions. In the current work, a 4-class SSVEP-based BCI system was set up. Ten subjects participated and EEG was recorded from 21 channels overlying occipital areas. Features were extracted by applying Discrete Fourier transformation and a lock-in analyzer system. A simple one versus the rest classifier was applied to compare methods and localize individual electrode positions. It was shown that the use of three SSVEP-harmonics recorded from individual channels yielded significantly higher classification accuracy compared to one harmonic and to the standard positions O1 and O2. Furthermore, the application of a simple one versus the rest classifier and the use of a lock-in analyzer system lead to a higher classification accuracy (mean+/-S.D., about 74+/-16%) in a 4-class BCI compared to the commonly used Discrete Fourier transformation (DFT, 62+/-14%). By applying a screening procedure, the optimal electrode positions for bipolar derivations can be detected. Furthermore, information about subject's specific 'resonance-like' frequency regions can be obtained by observing higher harmonics of the SSVEPs.

A 0.35microm CMOS integrated circuit for multi-channel neuronal recording with twelve true-differential channels, band separation and digital offset calibration is presented. The measured signal is separated into a low-frequency local field potential and high-frequency spike data. Digitally programmable gains of up to 60 and 80 dB for the local field potential and spike bands are provided. DC offsets are compensated on both bands by means of digitally programmable DACs. Spike band is limited by a second order low-pass filter with digitally programmable cutoff frequency. The IC has been fabricated and tested. 3microV input referred noise on the spike data band was measured.

This paper describes the circuitry and construction of a novel electronic threshold discriminator, and details its specific application to in vivo intracellular recording. The discriminator reliably triggers electrophysiological recording at pre-selectable membrane potentials in neuronal systems that exhibit membrane potential oscillations. It has been used successfully whilst recording from spiny projection neurons of the striatum to measure membrane properties and trigger electrical stimulation within either of two discrete membrane potential "states". The device works by comparing the analogue membrane potential waveform with a user-defined threshold membrane potential, and outputs a logic signal to flag the occurrence of a threshold-crossing event. This signal is used to trigger the commencement of episodic recording and the application of current injection or electrical stimulation at a consistent membrane potential. Thus, the discriminator acts as a functional clamp to isolate evoked responses from endogenous fluctuations in membrane potential. The unit uses cheap and easily available components and can be constructed with the minimum of electronics experience. It could be adapted to isolate discrete events within any oscillatory system.

The cost of electronic equipment can be a critical barrier to including neurophysiology exercises in biology teaching programs. We describe the construction of a simple and inexpensive AC preamplifier with performance comparable to that of commercial products. The amplifier consists of two integrated circuits in five stages: differential input, fixed gain, variable gain (100 or 1000), low-pass filter (5 or 20 kHz), and 50 or 60 Hz notch filter. We compared our amplifier with two commercial units, the A-M Systems Model 1700 and the Grass P15. The quality of extracellular recording from a typical student preparation (spontaneously active crayfish motor nerve) was the same for all three amplifiers, although our amplifier has slightly higher internal noise than the P15 and slightly lower common-mode rejection than the 1700 and P15. In addition, we describe a simple suction electrode for extracellular nerve recording. It is easily constructed from readily available materials and uses a disposable plastic pipette tip, instead of the traditional glass tip, to contact the nerve. This tip is easily replaced if broken or clogged, and can be adapted to different recording conditions by selecting a different tip size or stretching the plastic. Development of this equipment is part of an ongoing project to promote neuroscience education by expanding the neurophysiology options available to laboratory instructors.

Microneurography was introduced in 1967 and has developed into an invaluable tool for investigating human somatosensory, motor and cardiovascular physiology and pathophysiology. It involves percutaneous insertion of a metal microelectrode into fascicles of limb and facial nerves. This review covers the procedures and equipment necessary for microneurography and provides a current circuit for a preamplifier. Evidence is presented that (i) most recordings from myelinated axons involve an effective penetration of the myelin by the electrode; (ii) based on physiological criteria, microstimulation through the electrode can be used to activate single axons although the probability of this is relatively low and (iii) despite `micro' lesions caused by the electrode insertion into the nerve and its fascicles, the morbidity with the procedure is acceptably low.

A 2-channel action-potential generator system was designed for use in testing neurophysiologic data acquisition/analysis systems. The system consists of a personal computer controlling an external hardware unit. This system is capable of generating 2 channels of simulated action potential (AP) waveshapes. The AP waveforms are generated from the linear combination of 2 principal-component template functions. Each channel generates randomly occurring APs with a specified rate ranging from 1 to 200 events per second. The 2 trains may be independent of one another or the second channel may be made to be excited or inhibited by the events from the first channel with user-specified probabilities. A third internal channel may be made to excite or inhibit events in both of the 2 output channels with user-specified rate parameters and probabilities. The system produces voltage waveforms that may be used to test neurophysiologic data acquisition systems for recording from 2 spike trains simultaneously and for testing multispike-train analysis (e.g., cross-correlation) software.

The use of voltage clamp with a single electrode has been useful in estimating kinetic parameters for a number of ionic whole-cell currents. There are two main types of such a technique: discontinuous voltage clamp (dSEVC) (Brennecke and Lindemann, 1974), and continuous voltage clamp (cSEVC) (Hamill et al., 1981). We have studied, by means of computer simulations, the performance of both types of clamp on estimating activation kinetics parameters of a typical neuronal Ca2+ current. Deviations from the theoretical values are shown to be sensitive on both set-up and cell properties. Both types of clamp are shown to lose voltage control when either access resistance or absolute membrane conductance are increased. In contrast, changes in membrane capacitance affect differently to the estimates obtained by the two types of clamp. Cell size is also shown to affect cSEVC performance but not that of dSEVC. The nature and magnitude of errors obtained by using both types of clamp in different situations are discussed.

This paper describes in detail the construction of a low-noise optically isolated preamplifier for recording extracellular action potentials from nerve cell bodies and axons. This preamplifier is less prone to pick up noise from extraneous sources of electromagnetic radiation than non-isolated designs.

Microelectrode recording arrays of 60–100 electrodes are commonly used to record neuronal biopotentials, and these have aided our understanding of brain function, development and pathology. However, higher density microelectrode recording arrays of larger area are needed to study neuronal function over broader brain regions such as in cerebral cortex or hippocampal slices. Here, we present a novel design of a high electrode count picocurrent imaging array (PIA), based on an 81,920 pixel Indigo ISC9809 readout integrated circuit camera chip. While originally developed for interfacing to infrared photodetector arrays, we have adapted the chip for neuron recording by bonding it to microwire glass resulting in an array with an inter-electrode pixel spacing of 30 μm. In a high density electrode array, the ability to selectively record neural regions at high speed and with good signal to noise ratio are both functionally important. A critical feature of our PIA is that each pixel contains a dedicated low noise transimpedance amplifier (∼0.32 pA rms) which allows recording high signal to noise ratio biocurrents comparable to single electrode voltage amplifier recordings. Using selective sampling of 256 pixel subarray regions, we recorded the extracellular biocurrents of rabbit retinal ganglion cell spikes at sampling rates up to 7.2 kHz. Full array local electroretinogram currents could also be recorded at frame rates up to 100 Hz. A PIA with a full complement of 4 readout circuits would span 1 cm and could acquire simultaneous data from selected regions of 1024 electrodes at sampling rates up to 9.3 kHz.

A Macintosh-based system is described for performing instrument control, data acquisition and storage operations in single-electrode whole-cell voltage clamp experiments. The system consists of a commercially available voltage clamp amplifier, multifunction input/output (I/O) board, graphical programming language (LabVIEW 2) and custom built 'virtual instrument' (VI). The I/O board is capable of fast (up to 110 ksample/s) multichannel analog-to-digital (A/D) conversion with 12-bit resolution. It can control the gain settings of the clamp unit through digital I/O lines and generate the P/N leak subtraction protocol to eliminate the linear portion of capacitive currents using analog output voltages and gating pulses. Complete voltage clamp protocols can be implemented using the on-screen front panel controls of the VI. It enables the user to visualize the acquired data, to graph sets of current-voltage (I-V) relations or to fit single-exponential functions to one current trace. To evaluate the adequacy of whole-cell recording, the total membrane capacitance (Cm), the series resistance (Rs) and the time constant (tau c) of the decay of the capacitive current are calculated using the single-exponential function fit to the data. The system is particularly well suited to the study of large quantities of transmembrane I-V relationships. Source code for the crucial elements of the VI as well as sample recordings from a cultured spinal cord neuron, illustrating system operation, are presented.

Artifact from electrical stimulation imposes a problem for the recording of physiological responses to electrical stimulation. Here we describe a simple, low-cost, gated differential amplifier for the recording of physiological responses to electrical stimulation. The gain of the amplifier is set to 1 during electrical stimulation by setting the gate input to a high logic state to avoid overloading of the amplifier by the artifact. Following electrical stimulation, the gate input is set to a low logic state, resulting in a gain of 1000 for frequencies between 300 Hz and 25 kHz (-3 dB points). The gain at low frequencies (0-0.2 Hz) is held constant at 1 to avoid transients in the output signal arising from changes in gain at these frequencies. The gain of the amplifier following stimulation (gate low) was independent of the magnitude of the artifact and was therefore suitable for the measurement of neural field potentials with low impedance electrodes.

The design of a simple and inexpensive battery powered lamp controller for microscope lamps commonly used in patch clamp and other biophysical studies is described. The circuit linearizes the normally exponential voltage-intensity curve of standard 12-V lamps by using an operational amplifier to provide feedback to the drain of a power MOSFET. When the unit is turned off, a charging circuit recharges the battery at a constant potential until the battery voltage reaches a preset level. The charging voltage is then reduced to balance the self-discharge rate of the battery.

Research into the neuromechanical basis of behavior, either in biomechanics, neuroethology, or neuroscience, is frequently limited by methods of data collection. Two of the most pressing needs are for methods with which to (1) record from multiple neurons or muscles simultaneously and (2) perform this recording in intact, behaving animals. In this paper we present the fabrication and testing of flexible multielectrode arrays (fMEAs) that move us significantly towards these goals. The fMEAs were used to record the activity of several distinct units in the coxa of the cockroach Blaberus discoidalis. The devices fabricated here address the first goal in two ways: (1) their flexibility allows them to be inserted into an animal and guided through internal tissues in order to access distinct groups of neurons and muscles and (2) their recording site geometry has been tuned to suit the anatomy under study, yielding multichannel spike waveforms that are easily separable under conditions of spike overlap. The flexible nature of the devices simultaneously addresses the second goal, in that it is less likely to interfere with the natural movement of the animal.

'Common Electrode' microneurography (i.e. stimulating a nerve and recording return afferent neural activity through the same microelectrode facilitates investigation of linkages between sensory and motor nervous systems in humans. Currently there is no commercial product designed specifically to conduct common electrode microneurography experiments. However, such experiments would advance investigations in several key areas including spinal injury research. In this paper, we report on the successful production and testing (on a human subject) of an integrated amplifier built specifically for this purpose. The amplifier was built using commercially available components to allow for both easy and economical manufacture. In particular, we report on the design requirements and outline our chosen design solutions. The amplifier handles low-level neural signals amidst large 50 Hz interference, with protection against potentially high stimulation voltages of over 100 V dc, with minimal cross-coupling of rapid stimulus pulses onto the high gain amplifier's input, and a short 'blocking' time between stimulation and recording. The amplifier also includes necessary filters, selectable gains and internal stimulator triggering circuits to provide a simple, integrated solution for common electrode operation on human subjects. © 2005 Elsevier B.V. All rights reserved.

We present the design and testing of a 16-channel analog amplifier for processing neural signals. Each channel has the following features: (1) variable gain (70–94 dB), (2) four high pass Bessel filter poles ( f −3 dB =445 Hz), (3) five low pass Bessel filter poles ( f −3 dB =6.6 kHz), and (4) differential amplification with a user selectable reference channel to reject common mode background biological noise. Processed signals are time division multiplexed and sampled by an on-board 12-bit analog to digital converter at up to 62.5k samples/s per channel. The board is powered by two low dropout voltage regulators which may be supplied by a single battery. The board measures 8.1 cm ×9.9 cm, weighs 50 g, and consumes up to 130 mW. Its low input-referred noise (1.0 μVRMS) makes it possible to process low amplitude neural signals; the board was successfully tested in vivo to process cortically derived extracellular action potentials in primates. Signals processed by this board were compared to those generated by a commercially available system and were found to be nearly identical. Background noise generated by mastication was substantially attenuated by the selectable reference circuit. The described circuit is light weight and low power and is used as a component of a wearable multichannel neural telemetry system.

Display systems based on conventional computer graphics cards are capable of generating images with about 8-bit luminance resolution. However, most vision experiments require more than 12 bits of luminance resolution. Pelli and Zhang [Spatial Vis. 10 (1997) 443] described a video attenuator for generating high luminance resolution displays on a monochrome monitor, or for driving just the green gun of a color monitor. Here we show how to achieve a white display by adding video amplifiers to duplicate the monochrome signal to drive all three guns of any color monitor. Because of the lack of the availability of high quality monochrome monitors, our method provides an inexpensive way to achieve high-resolution monochromatic displays using conventional, easy-to-get equipment. We describe the design principles, test results, and a few additional functionalities.

The human brain is dominated by the neocortex, a large folded surface, whose cellular and synaptic elements are arranged in layers. Since cortical structure is relatively constant across its surface, local information processing can be inferred from multiple laminar recordings of its electrical activity along a line perpendicular to its surface. Such recordings need to be spaced at least as close together as the cortical layers, and need to be wideband in order to sample both low frequency synaptic currents as well as high-frequency action potentials. Finally, any device used in the human brain must comply with strict safety standards. The current paper presents details of a system meeting these criteria, together with sample results obtained from epileptic subjects undergoing acute or chronic intracranial monitoring for definition of the epileptogenic region.

A miniature telemetric system is described which allows simultaneous measurements of neural activity and vocalization in freely moving monkeys within their social group. Single and multi-unit activities were detected with medium impedance electrodes that were fixed to self-made microdrives allowing accurate vertical positioning over a range of 8 mm. Vocalizations were registered by means of a piezo-ceramic device sensing the vocalization-induced skull vibrations. This allowed identification of the vocalizing animal in a larger group and eliminated environmental noise. Neuronal activity and vocalization were transmitted via separate channels of a FM transmitter using different carrier frequencies. The signals were decoded in two conventional FM receivers equipped with an automatic frequency control. The signals were stored for off-line analysis on a HiFi-videotape recorder.

Single electrode whole cell current- and voltage-clamp techniques in conjunction with intra- and extracellular phoresis and extracellular application of pharmacological agents were applied to study neurons in deep layers of the brainstem of anesthetized, paralyzed and artificially ventilated cats. We compared slow rhythmic changes and stimulus-evoked postsynaptic current and voltage responses of neurons as they were recorded with fine-tipped microelectrodes filled with 2-3 M 'microelectrode solutions' or with 0.3 M 'patch solutions', or with patch electrodes. The experimental data were then compared with the effects of somatic and dendritic conductance changes simulated in a cell model. A new method was introduced for alternating current and voltage-clamp measurements performed at 300 Hz, which provided quasi-simultaneous measurements of slow changes of spontaneous synaptic currents and potentials. During current or voltage clamp, chemicals which affect voltage- and receptor-controlled conductances were ionophoresed intracellularly through single or theta-type glass electrodes. We show examples of activation of low-voltage activated Ca2+ responses after blockade of Na+ currents by intracellular QX 314 and K+ currents by intracellular Cs+ injections in addition to Sp-cAMPs to activate protein kinase A. TEA, NMDA and GABA were used to demonstrate the effectiveness of extracellular application of drugs through multibarrel electrodes or local application through a 'bath'. The various tests demonstrated that single electrode whole cell current- and voltage-clamp methods, in combination with various techniques for drug application, can be well applied to study the biophysical properties and pharmacological sensitivities of neurons embedded in in vivo networks within deep layers of the brain.

A Macintosh-based system performs stimulus control and data acquisition, and an off-line analysis, in experiments on visually driven neurons in frog. The stimulus is a target moved on a modified XY recorder. The computer is cquipped with a multifunction input/output board to perform stimulus control and data acquisition. The graphical programming system LabVIEW 2 was used to develop the ‘Vision 93’ package made of 4 main ‘virtual instruments’ (VIs). By means of docs - E xp, the user controls the experiment via screen displays which look like front panels of electronic instruments. docs - p reprot performs a user-controlled spike detection and computes mean impulse rate values. docs - sas displays the instantaneous frequency, mean impulse rate, spike counts or interspike time intervals as staircase histograms and/or spline smoothed curves. Finally, docs - x - f unctions computes and graphs quantitative stimulus/response relationships in terms of velocity, diameter, orientation and configuration of the target. The functionalities of these main VIs are presented and original software components are detailed. System operation is illustrated by using the successive VIs to process a sample signal record.

Using silicon-integrated circuit technology, we have fabricated a flexible multi-electrode array and used it for measuring evoked potentials at the surface of the ferret primary auditory cortex (AI). Traditionally, maps of cortical activity are recorded from numerous sequential penetrations with a single electrode. A common problem with this approach is that the state of the cortex (defined in part by level of anesthesia and number of active cells) changes during the time required to generate these maps. The multi-electrode array reduces this problem by allowing the recording of 24 locations simultaneously. The specific array described in this report is designed to record cortical activity over a 1 mm 2 area. It is comprised of 24 gold electrodes (40 × 40 μm 2 ) each spaced 210 μm apart. These electrodes are connected to contact pads via gold leads (5 cm in length). The electrodes, leads, and contact pads are sandwiched between two layers of polyimide. The polyimide passivates the device and makes the device flexible enough to conform to the shape of the cortex. The fabrication procedures described here allow various other layouts and areas to be readily implemented. Measurements of the electrical properties of the electrodes, together with details of the multichannel amplification, acquisition, and display of the data are also discussed. Finally, results of AI mapping experiments with these arrays are illustrated.

A software-based system for real-time measurement of membrane capacitance was developed for monitoring exocytosis in a single cell. The IBM PC compatible software, linked to an interface box, provides capacitance measurement capabilities to a patch-clamp setup utilizing a Labmaster data acquisition board. In order to measure the time-dependent changes in membrane capacitance, the system uses a software-based phase detector which isolates capacitive membrane current from a cell subject to sinusoidal voltage stimulation. The sampling program can monitor changes in membrane capacitance in response to depolarizing voltage steps, intracellular calcium stimulation, or drug application. A separate analysis program was constructed to implement the quantitative analysis, plotting and exporting of the capacitance, conductance and current data acquired by the sampling program.

The electrical self-stimulation paradigm has proven to be very useful in research aimed at delineating the neural substrates involved in reward-related learning. Of the procedures currently employed the curve-shift method is among the more useful since it distinguishes between treatment effects on reward and performance. This method involves generating and plotting rate-frequency functions and quantifying the effects of experimental manipulations on reward by measuring the degree of lateral shift in these functions. We have designed a computerized system that automatically generates and collects descending rate-frequency functions from self-stimulating rats. The 3 main units of this system consisted of a 6809 micro-controller, a programmable timer logic board and a constant current source. The micro-controller and programmable timer operated on custom written software that monitored lever pressing in the operant chambers and controlled stimulation parameters to generate and record rate-frequency functions. The present report describes this system and presents some typical data collected from rats self-stimulating on ventral tegmental electrodes before and after the administration of intra-accumbens vehicle (0.5 microliter distilled H2O), (+)-amphetamine (20.0 micrograms/0.5 microliter), quinpirole (10.0 micrograms/0.5 microliter) and systemic quinpirole (1.0 mg/kg), all dopamine agonists. Stimulation consisting of 300-ms trains of cathodal rectangular pulses (0.1 ms) was available in 50-s trials. The number of pulses per train was decreased logarithmically from a value that sustained maximal responding to one that would not sustain responding. Self-stimulation thresholds were obtained by fitting the Gompertz growth model to the data and calculating the point of maximal acceleration of the sigmoidal curve. It was found that the present system generated and collected rate-frequency functions similar to those that have been obtained manually in previous experiments. The data showed that the system was sensitive to both central and systemic pharmacological manipulations by producing lateral and vertical shifts of the rate-frequency functions, indications of reward and motor effects, respectively. It was concluded that the present design was useful in conducting entire self-stimulation sessions that required minimal monitoring by the experimenter.

We describe a fast, automated system for the measurement of righting reflex latencies in drug studies. This system, which we call a 'tolerometer', is especially useful for studies of drug tolerance which require a simple measurement of motor behaviour on a daily basis, for long periods of time. The tolerometer consists of a semi-cylindrical platform positioned on a 2 kg load cell, connected to a strain gauge amplifier (Radio Spares Ltd). The output from the amplifier is connected to a MacLab data acquisition system (Analog Digital Instruments), controlled by a Macintosh Classic computer. The MacLab Chart program is used to display, on the Macintosh screen, the load changes which occur during a righting reflex; sampling frequencies up to 40 kHz can be used, but we find 20-100 Hz adequate. Using measurement cursors provided by the Chart program, the latency from the point at which an animal is placed on the tolerometer platform in the supine position, until the completion of a righting reflex, can be measured accurately and easily.

A modification of a commercially available digital-audio tape (DAT) for DC recordings such as those used in patch clamp and other electrophysiological experiments is introduced. The modified DAT can record data from 2 channels plus a separate trigger signal for up to 2 h. The bandwidth ranges from direct current to 21 kHz; the signal-to-noise ratio is above 90 dB and the A-D resolution is 16 bit. A 120-min cassette yields a storage capacity of 1.4 Gbytes. The trigger is ·hidden’ on 1 channel as a burst of 1-ms duration, thus minimizing interference with the recorded data. The modified DAT offers a low-cost yet high quality solution to most analog data storage needs.

An integrated system for recording and analyzing electrophysiological data from multiple channels is described. The system uses an MS-DOS microcomputer, a 16-channel amplifier, and multiple-tipped electrode arrays designed for use in intact and slice preparations. The system is designed for applications where the collection and analysis of multiple-channel electrophysiological data is desirable, including the construction of current source density (CSD) profiles from field potential data. The software incorporates on-line averaging, CSD and freeze-frame capabilities to guide the experiment in progress. Additional off-line analyses include multiple unit activity, power spectra, and automatic scans of data files for peak amplitude, area, latency, and slope within user-defined latency windows. All data and analyses can be exported to commercial statistical/graphical programs for the creation of publication-ready figures.

Fast cyclic voltammetry is a new voltammetric technique which has been especially useful for measurements of dopamine release in vivo. This paper describes methods for the construction of a basic fast cyclic voltammetric amplifier, and the associated apparatus necessary to carry out fast cyclic voltammetric experiments.

Patch-clamping is an established method for directly measuring ionic transport through cellular membranes with sufficient resolution to observe open/close transitions of individual channel molecules. This paper describes an alternative technique for patch-clamping which uses a capacitor as the transimpedance element. This approach eliminates bandwidth and saturation limitations experienced with resistive patch-clamping amplifiers. A complete monolithic design featuring an on-chip operational amplifier, a capacitor array with gain-ranging from 30 pF down to 0.03 pF, and reset and gain ranging switches has been fabricated using 5 microns CMOS technology. It is shown that the voltage noise of the CMOS operational amplifier limits the overall noise performance, but that performance competitive with conventional instruments can be achieved over a 10 kHz bandwidth, at least for small input capacitances (less than or equal to 5 pF). Results are presented along with an analysis and comparison of noise performance using both resistive and capacitive elements.

The advantages of utilizing a microprocessor design kit as a central element in custom laboratory instrumentation are demonstrated in the design of a real-time, multiple point, tissue displacement monitor. The tissue sample to be monitored is submerged in a saline bath, through which perpendicular electric fields are alternately generated. Analog displacement data are generated by differentially amplifying the voltage between each of 4 sense electrodes attached to the tissue surface, and a reference electrode, positioned on the tissue surface central to the sense electrodes. The microprocessor unit is used to control field generation, to multiplex the sensing electrode signals through the analog signal processing electronics, and, after analog-to-digital conversion, to scale and interface the digital displacement data to a host processor.

A system has been developed for measuring the three-dimensional (3D) isometric forces produced by the arm in response to a visual stimulus. The output of 3 load cells is combined to determine the components of the 3D response force. The maximum force range of the load cells is 2000 g which can be read with a resolution of 4 g and with a measured accuracy of +/- 10 g. An overload stop protects the device to a load of 23 kg. The visual instruction to the subject concerning the direction and magnitude of the 3D force vector to be produced is presented using a vivid spherical stereogram. This stereogram is produced using the anaglyphic technique where the left and right images are separated by color filters. A dense aggregation of points defines the target cursor, which can be positioned anywhere inside or on the surface of the sphere. This cursor can represent a stationary or a moving target. A force feedback cursor can be provided to indicate to the subject his/her response. The color display on the cathode ray tube is produced by a display generator driven by a computer.

A technique has been developed to record from 16 different brain sites of the freely moving rat using subminiature MOSFET preamplifiers. The high input impedance, small size, durability and light weight of the amplifiers and connecting cable allows high quality multisite recording of field potentials and unit activity. In addition, a movable headstage for positioning multiple microelectrodes is described. The compact recording system permits one to construct neocortical EEG maps, instant depth profiles of evoked and spontaneous field data, and to study neuronal synchrony of distant cell populations.