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PubMed1984

An array of microelectrodes to stimulate and record from cardiac cells in culture.

An array of extracellular microelectrodes containing 25 recording and 6 stimulating electrodes was fabricated using microelectronics technology. Ventricular myocardial cells from 8- to 10-day chick embryos were cultured on the surface of the microelectrode array. Extracellular potentials were recorded simultaneously from multiple sites. Simultaneous recordings of extracellular and transmembrane potentials were made from single sites. Extracellular potentials were also recorded simultaneously with cell motion from single sites. Cells were paced by means of electrical stimuli applied via the stimulating electrodes. Conduction velocity in a strip of cells varied linearly as a function of temperature from 0.21 m/s at 26 degrees C to 0.38 m/s at 36.5 degrees C.

Animals↗
PubMed1981

Vasopressin, theophylline, PGE2, and indomethacin on active Na transport in frog skin: studies with microelectrodes.

Active transepithelial Na transport in frog skin is influenced by vasopressin, theophylline, indomethacin, and PGE2. During stimulation or inhibition of the short-circuit current, the transapical membrane voltage of short-circuited skins was recorded using an intracellular microelectrode. The microelectrode also permitted determination of the fractional resistance of the apical barrier of the cells (fRo) and the E'1 (transepithelial voltage at which the apical membrane voltage is zero). Analysis of the data according to an electrical model proposed previously indicated that changes of ISC were mediated primarily via changes of the slope resistance Rfo (Vo negative) of the apical barrier of the cells with little or no effect on the Thévenin emf or resistance of the basolateral membranes. These data are in accordance with previous observations that ADH had no effect on the ENa and are discussed in relation to the origin of the ENa at the basolateral membranes of the epithelial cells.

Animals↗
PubMed1984

Characterization of apical cell membrane Na+ and K+ conductances of cortical collecting duct using microelectrode techniques.

The apical cell membrane ionic conductive properties of the isolated perfused rabbit cortical collecting duct (tubule) were assessed at 37 degrees C using microelectrode techniques. In the initial evaluation of the methodology, it was observed that stable cell membrane voltage recordings could be obtained by impaling cells either from the luminal side across the apical cell membrane or from the bath side across the basolateral cell membrane, providing initial evidence supporting the application of these techniques to this tissue. With the latter method of impalement, it was observed that addition of amiloride (50 microM) to the luminal perfusate caused a hyperpolarization of the apical cell membrane voltage, a decrease in the transepithelial conductance, and an increase in the fractional resistance (estimated as the ratio of the resistance of the apical cell membrane to the sum of apical and basolateral cell membrane resistances). These results are consistent with an amiloride-sensitive Na+ conductance at the apical cell border. In a similar manner it was deduced from the effects of elevating K+ in the luminal perfusate from 5 to either 25 or 50 mM that there was a high K+ conductance at the apical border. This conductive pathway was blocked by the luminal addition of 5 mM Ba2+ or reduction of the luminal pH to 4.0. Furthermore, since addition of both amiloride and Ba2+ to the perfusate caused the fractional resistance to increase from 0.52 +/- 0.04 to 0.91 +/- 0.03, the Na+ and K+ conductances are the apparent dominant conductive pathways at that border. It is concluded that microelectrode techniques can be applied successfully to the cortical collecting duct and that the apical cell membrane possesses an amiloride-sensitive Na+ conductance and a Ba2+- and H+-sensitive K+ conductance.

Amiloride↗
PubMed1986

Measurement of intracellular pH with microelectrodes in rat kidney in vivo.

The construction of two types of double-barreled microelectrodes of sufficiently small tip size to record cytosolic pH (pHc) in renal tubular epithelial cells is described. Mean pHc in control anesthetized rats was 7.10 and mean basolateral membrane potential (Em) was -51.8 mV. These results suggest that hydrogen ions are actively extruded from either or both poles of the proximal tubular cell but that bicarbonate exit across the basolateral membrane is passive. In animals treated with acetazolamide, pHc was significantly elevated (mean 7.35) but Em was unchanged, suggesting that proton extrusion continues but that the rate of reaction of OH- with CO2 is diminished due to carbonic anhydrase inhibition. A pH higher than that of arterial blood was obtained from sites presumed to be in the interstitium. The evidence for the various assignments of microelectrode tip position is discussed.

Acetazolamide↗
PubMed1987

In vivo measurement of tubular fluid ferrocyanide with carbon-fiber microelectrodes.

Techniques to construct carbon-fiber microelectrodes and to measure ferrocyanide ion concentration in single nephrons are described. The measurement involves polarizing an inert carbon-fiber microelectrode 500 mV positive with respect to a Ag-AgCl reference, while measuring the faradic current produced by the oxidation of ferrocyanide. A carbon fiber (5-7 micron diam) is heat sealed into a glass micropipette that is then sharpened, silanized, and electrochemically pretreated to minimize electrode degradation by protein. Circuit diagrams for an inexpensive voltage clamp-current monitor and a data sampling device are presented. The electrodes show a linear response to changes in ferrocyanide concentration in large and very small (20 nl) volumes in vitro. The electrodes were used in an electrochemical microassay to determine tubular fluid-to-plasma ferrocyanide concentration ratios and nephron filtration rates with proximal micropuncture samples. The results show excellent agreement with paired determinations using [3H]inulin. In vivo proximal tubule perfusion experiments show a rapid linear response to changes in tubular fluid ferrocyanide concentration. These electrodes permit rapid quantitative measurements of ferrocyanide concentration and water transport in the proximal tubule and may be useful in other biological systems.

Animals↗
PubMed1983

Changes in brain ECF pH during metabolic acidosis and alkalosis: a microelectrode study.

We used pH-sensitive double-barreled microelectrodes to measure brain extracellular fluid (ECF) pH in anesthetized dogs during isocapnic infusion acidosis (HCl) and alkalosis (Na2CO3) of 45-60 min duration. The diameter of the tips of these electrodes varied from less than 1 to 27 micron and were placed 5 mm below the surface of the parietal cortex. In group I (metabolic acidosis, n = 5) mean plasma and brain ECF pH fell significantly by 0.221 and 0.025, respectively, with changes in brain ECF pH being 11.3% of those noted in plasma. In group II (metabolic alkalosis, n = 5) mean plasma and brain ECF pH rose significantly by 0.170 and 0.049, respectively, with changes in brain ECF pH being 28.8% of those noted in plasma. Mean arterial and sagittal venous PCO2 and cisternal cerebrospinal fluid (CSF) acid-base variables did not change significantly during acid or base infusion. We conclude that during transients of isocapnic metabolic acid-base perturbations ionic gradients exist between brain ECF and CSF and that changes in brain ECF pH measured by microelectrodes follow the changes in plasma pH. These pH changes may play an important role in respiratory adaptations of acute metabolic acidosis and alkalosis.

Acidosis↗
PubMed1987

Improved fabrication of double-barreled recessed cathode O2 microelectrodes.

Polarographic recessed cathode gold microelectrodes are the preferred type of O2 microelectrode for tissue measurements, but the method originally described for their construction is difficult. An improved method of constructing such electrodes consists of several steps: 1) insertion of a rod made of a special low-melting point alloy into a pulled glass micropipette, 2) heating of the electrode tip as the alloy is pushed toward the tip, 3) beveling, and 4) gold plating the alloy, leaving a recess of the desired length. This method can be used to make single- or double-barreled electrodes in which the O2 barrel is as small as 2-3 micron. The electrodes retain their characteristics for several weeks.

Equipment Design↗
PubMed2006

Fabrication and use of high-speed, concentric h+- and Ca2+-selective microelectrodes suitable for in vitro extracellular recording.

Ion-selective microelectrodes (ISMs) have been used extensively in neurophysiological studies. ISMs selective for H(+) and Ca(2+) are notable for their sensitivity and selectivity, but suffer from a slow response time, and susceptibility to noise because of the high electrical resistance of the respective ion exchange cocktails. These drawbacks can be overcome by using a "coaxial" or "concentric" inner micropipette to shunt the bulk of the ion exchanger resistance. This approach was used decades ago to record extracellular [Ca(2+)] transients in cat cortex, but has not been subsequently used. Here, we describe a method for the rapid fabrication of concentric pH- and Ca(2+)-selective microelectrodes useful for extracellular studies in brain slices or other work in vitro. Construction was simplified compared with previous implementations, by using commercially available, thin-walled borosilicate glass, drawing an outer barrel with a rapid taper (similar to a patch pipette), and by use of a quick and reliable silanization procedure. Using a piezoelectric stepper to effect a rapid solution change, the response time constants of the concentric pH and Ca(2+)-electrodes were 14.9 +/- 1.3 and 5.3 +/- 0.90 ms, respectively. Use of these concentric ISMs is demonstrated in rat hippocampal slices. Activity-dependent, extracellular pH, and [Ca(2+)] transients are shown to arise two- to threefold faster, and attain amplitudes two- to fourfold greater, when recorded by concentric versus conventional ISMs. The advantage of concentric ISMs for studies of ion transport and ion diffusion is discussed.

Animals↗
PubMed2004

Spatial reconstruction of trajectories of an array of recording microelectrodes.

We present a method for estimating the locations of sites visited by an array of microelectrodes. The method relies on visualization of tracks made by electrodes coated in a fluorescent dye. These tracks are used to estimate the parameters of a simple geometrical model that generates coordinates for each recording site. We describe several ways to measure the error of this procedure and present experimental results from recordings in the motor cortex of macaque monkeys that suggest that errors are of the order of 230 microm. We also introduce a coordinate transformation that takes into account the convoluted structure of the cortex near sulci to conveniently visualize recording site locations in a rectilinear representation. This method greatly extends the capabilities of microelectrodes for studying the three-dimensional structure of topographic maps in the cortex.

Animals↗
PubMed2004

A multi-channel, implantable microdrive system for use with sharp, ultra-fine "Reitboeck" microelectrodes.

Arrays of closely spaced quartz-insulated, platinum-tungsten microelectrodes are widely used to obtain acute recordings from chronically prepared subjects. These electrodes have excellent recording characteristics and can be fabricated to a wide variety of tip specifications. Typically, in such experiments, electrodes are introduced into, and removed from, the brain on a daily basis and, over many months of study, hundreds of penetrations may be made through an intact dura. This procedure has benefits as well as problems and risks. For some experimental aims, it might be desirable to leave the microelectrodes within the brain so that the penetrations could be continued on subsequent days. This would allow a more thorough and systematic exploration of the neurons that lie along the trajectory of each of the closely aligned electrodes and would minimize risks and preparation time associated with daily electrode insertions. Here we present a means for achieving this aim using arrays of sharp, flexible Reitboeck electrodes of extremely fine diameter (40-microm shaft diameter, pulled and ground to a fine tip). We show that these electrodes retain their excellent recording characteristics and can remain under microdrive control within the brain for periods of many months and, in one remarkable case, for >4 years.

Action Potentials↗
PubMed1996

Positive feedback from hilar mossy cells to granule cells in the dentate gyrus revealed by voltage-sensitive dye and microelectrode recording.

1. Microelectrode recording and fluorescence measurement with voltage-sensitive dyes were employed in horizontal hippocampal slices from rat to investigate responses in the dentate gyrus to molecular layer and hilar stimulation. 2. Both field potential and dye fluorescence measurement revealed that electrical stimulation of the molecular layer produced strong excitation throughout large regions of the dentate gyrus at considerable distances from the site of stimulation. 3. Treatment of slices with the excitatory amino acid receptor antagonists 6,7-dinitroquinoxaline-2,3-dione (DNQX) and (+/-)-2-amino-5-phosphonovaleric acid (APV) unmasked dye fluorescence signals in the outer and middle molecular layers corresponding to action potentials in axons, presumably belonging to the perforant path. The spread of these axonal signals away from the site of stimulation was far less extensive than the spread of control signals through the same regions before blockade of excitatory synapses. Large control responses could be seen in regions distant from the stimulation site where the axonal signals were not detectable. A lack of correlation between control signals and axonal signals revealed by DNQX and APV supports the hypothesis that responses in distal regions of the molecular layer were not dependent on perforant path axons. 4. The perforant path was cut by producing a lesion in the outer two-thirds of the molecular layer. Both dye fluorescence and microelectrode recording showed that stimulation on one side of the lesion could produce signals on the same side as well as across the lesion. The lesion did not block the spread of excitation through the molecular layer. Across the lesion from the site of stimulation, negative-going field potentials were observed to peak in the inner molecular layer, which is the major field of projection of hilar mossy cells. 5. Electrical stimulation in the hilus adjacent to the granule cell layer evoked dye fluorescence responses in the molecular layer. Stimulation at this site evoked negative-going field potentials that peaked in the inner molecular layer. These signals were sensitive to excitatory amino acid receptor antagonists but not to gamma-aminobutyric acid-A (GABAA) receptor antagonists. 6. Activation of excitatory amino acid receptors in the hilus by focal application of (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) and N-methyl-D-aspartic acid (NMDA) elicited negative-going field potentials in the granule cell layer and depolarization of granule cells. Field potentials were blocked by tetrodotoxin (TTX), indicating that they were not caused by direct activation of receptors on granule cells, but rather by synapses from hilar neurons on granule cells. 7. These results taken together with previous studies of hilar mossy cells suggest a fundamental circuit consisting of granule cells exciting hilar mossy cells, which then excite more granule cells. This circuit provides positive feedback and can be considered a form of "recurrent excitation" unique to the dentate gyrus. The robustness of this circuit in hippocampal slices under control conditions suggest that mossy cell excitation of granule cells could play an important role in the normal activity of the hippocampus, and, when inhibition is compromised, this circuit could contribute to the generation and spread of seizures.

2-Amino-5-phosphonovalerate↗
PubMed1999

Do microelectrode techniques increase accuracy or decrease risks in pallidotomy and deep brain stimulation? A critical review of the literature.

Several recent publications have stated that the use of microelectrode recording (MER) during pallidotomy or deep brain stimulation (DBS) contributes to decreasing risks and side effects of surgery, and that such a technique is a prerequisite for minimizing lesion size and for accurate placement of the stereotactic lesion or the DBS electrode. To evaluate the consistency of these statements, we reviewed hundreds of papers and congress reports on MER- and non-MER-guided procedures published since 1992. This review showed that MER groups published more often than non-MER groups. While side effects of surgery were not uncommon in both groups, the rate of severe complications, such as hematoma, and mortality appeared to be higher when microelectrodes were used, both in ablative surgery and in DBS procedures. Besides, the nonaccurate placement of lesions or DBS electrodes, as assessed on published MRI figures, was not uncommon in MER publications. Lesion volume was, when reported, not different in both techniques. The electrical parameters of stimulation of implanted electrodes in the thalamic ventral intermediate (Vim) nucleus for treatment of tremor were higher in MER-guided surgery. The available literature suggests that MER techniques may increase the risks of surgery without enhancing its accuracy, compared to MRI-based macrostimulation techniques. To date, there is no randomized trial by one and the same group on the use of micro- versus macroelectrodes in surgery for movement disorders. A prerequisite for such a trial in the future must imply that the investigators have an equal nonprejudiced attitude towards, and equal confidence and experience in, either technique. Since such a prerequisite does not exist so far in the functional stereotactic community, a critical and comparative study of the available literature remains the only way to evaluate the pros and cons of either technique, in terms of targeting accuracy and surgical complications.

Bibliometrics↗
PubMed1999

Staged functional neurosurgery using image fusion: electronic atlas and microelectrode recording at Dundee.

The unforgiving nature of the thalamus, the globus pallidus and the subthalamic nucleus necessitates precise localization of functional targets. This requires the total attention of both the patient and the surgeon. To maximize the concentration of the patient and provide the most accurate localization, we performed staged stereotactic functional procedures. The first stage was performed under general anesthesia to abolish any head movement. We fused CT and MRI images and correlated the fused images with a digitized Talairach brain atlas. We calculated the target coordinates and fixed a modified Bennett Sphere to the skull with the central hole defining the trajectory to the target. The surrounding 12 holes gave parallel trajectories to targets surrounding the anatomical target at 2-mm intervals. The second stage was performed at least a week later under local anesthesia. Microelectrode recording using three simultaneous channels was used to refine the target. Once the microelectrode recordings and macrostimulation confirmed the desired target, a lesion was created or an Activa neurostimulator was inserted. Our early results using this technique in 28 procedures (in 19 patients) indicate a good outcome in 86% and a technical failure in 1 patient.

Diagnostic Imaging↗
PubMed2001

Microelectrode findings in the thalamus in chronic pain and other conditions.

Functional neurosurgery usually requires physiological corroboration of the target site, particularly by eliciting characteristic responses to stimulation, or else by microelectrode recording of single cell responses to appropriate stimuli. Understanding pain physiology with both strategies has proven elusive, particularly microelectrode recording in response to noxious or thermal stimuli. The limited experience with stimulation and recording in pain pathways of the brain will be reviewed as well as the apparently pathophysiological observations made in certain patients with neuropathic pain.

Causalgia↗
PubMed2001

Microelectrode recording for pallidotomy: mandatory, beneficial or dangerous?

There is an active debate regarding whether pallidotomy should be performed with microelectrode recording or macroelectrode stimulation. A meta-analysis was performed on the published reports (1992-2000) of unilateral pallidotomy for Parkinson's disease to determine if the outcome or complications of this procedure significantly differed between these two techniques. Papers were excluded if they followed a cohort of less than ten patients, had follow-up less than three months, or included previously reported patients. There were no significant differences between the two techniques in improvement of dyskinesia (p = 0.66) or UPDRS motor score (p = 0.62). Microelectrode recording had a significantly higher (p = 0.012) intracerebral hemorrhage rate (1.3 +/- 0.4%) compared to macroelectrode stimulation (0.2 +/- 0.2%).

Brain Damage, Chronic↗
PubMed2003

Hemorrhagic complications of microelectrode-guided deep brain stimulation.

BACKGROUND: The incidence of intracranial hemorrhage occurring during microelectrode-guided implantation of deep brain stimulators (DBS) for movement disorders has not been well defined. We report the incidence of hemorrhage in a large series of DBS implants into the subthalamic nucleus (STN), thalamus (VIM) and internal globus pallidus (GPi). METHODS: All DBS procedures performed by a single surgeon (P.A.S.) between June 1998 and April 2003 were included in this study. Patients had postoperative imaging (MRI or CT) 4-24 h following surgery, and all hematomas >0.2 cm(3) in volume were noted and scored as symptomatic (associated with any new neurologic deficit lasting >24 h) or asymptomatic. RESULTS: The total number of lead implants was 357. There were 5 symptomatic hematomas and 6 asymptomatic hematomas. The relative risk of hematoma (any type) per lead implant was 3.1%. The incidence of hematoma by target site was 2.5% per lead for STN-DBS, 6.7% for GPi-DBS and 0% for VIM-DBS. CONCLUSION: The overall risk of intraoperative or early postoperative symptomatic hemorrhage with microelectrode-guided DBS, over all targets, was 1.4% per lead implant. The brain target had a significant effect on the risk of hemorrhage.

Cerebral Hemorrhage↗
PubMed2006

Automatic microelectrode recording analysis and visualization of the globus pallidus interna and stereotactic trajectory.

Locating deep brain neuronal structures is required to accurately place deep brain stimulation (DBS) electrodes during stereotactic surgery in patients with Parkinson's disease and other movement disorders. This study investigates the efficacy of automatic microelectrode visualization and analysis methods to help neurosurgeons locate target structures more objectively, consistently, and easily during surgery. Ten patients (4 males and 6 females) who underwent bilateral implantation of DBS electrodes in the globus pallidus interna (Gpi), from 2001 to 2003, at the Oregon Health and Science University and the Portland Veterans Administration Medical Center were included. We compared the efficacy of the microelectrode recording signal energy, power spectral density (PSD), marginal probability density (mPDF), autocorrelation function (ACF), and partial ACF. mPDF and PSD estimates most accurately indicated the borders of the GPi target structure.

Aged↗