High-quality recording of bioelectric events

A multichannel instrumentation amplifier, developed to be used in a miniature universal eight-channel amplifier module, is described. After discussing the specific properties of a bioelectric recording, the difficulties of meeting the demanded specifications with a design based on operational amplifiers are reviewed. Because it proved impossible to achieve the demanded combination of low noise and low power consumption using commercially available operational amplifiers, an amplifier equipped with an input stage with discrete transistors was developed. A new design concept was used to expand the design to a multichannel version with an equivalent input noise voltage of 0·35 μV RMS in a bandwidth of 0·1–100 Hz and a power consumption of 0·6 mW per channel. The results of this study are applied to miniature, universal, eight-channel amplifier modules, manufactured with thick-film production techniques. The modules can be coupled to satisfy the demand for a multiple of eight channels. The low power consumption enables the modules to be used in all kinds of portable and telemetry measurement systems and simplifies the power supply in stationary measurement systems.     

Neuronal activity in the globus pallidus of multiple system atrophy patients.

The pathophysiological changes in neural activity that characterize multiple system atrophy (MSA) are largely unknown. We recorded the activity of pallidal neurons in 3 patients with clinical and radiological features of MSA who underwent unilateral microelectrode-guided pallidotomy for disabling parkinsonism. Findings in these patients were compared with 4 control patients with a clinical diagnosis of Parkinson's disease (PD). The position, firing rates, and firing patterns of single neurons in the pallidal complex were analyzed in both MSA and PD patients. The mean spontaneous firing rate of neurons in the internal segment of the globus pallidus internus (GPii) was significantly lower in MSA than in PD patients. There were no significant differences between MSA and PD patients, however, in firing rates of neurons in the external globus pallidus (GPe) or in the external segment of GPi (GPie). In addition, no significant differences in firing pattern were found between MSA and PD patients. In conclusion, this study has shown that firing rates of neurons in GPii but not in GPie and GPe are different in MSA patients compared with that in PD patients, a finding that may reflect the poor clinical results of pallidotomy reported in patients with MSA.     

Ambulatory blood pressure in patients with Parkinson's disease without and with orthostatic hypotension

Non-invasive ambulatory recordings of blood pressure and heart rate were performed using a Spacelabs device during day and night periods in patients with Parkinson's disease with (n = 19) or without orthostatic hypotension (n = 19). In patients with orthostatic hypotension, the average systolic and diastolic blood pressure during the night (137 ± 5/80 ± 3 mmHg) was higher (p < 0.05) than during the day period (121 ± 3/76 ± 2 mmHg). In patients without orthostatic hypotension, a decrease in blood pressure was recorded during the nocturnal period. In patients with orthostatic hypotension, the blood pressure variability was higher (p < 0.05) during the day (systolic: 14.6 ± 1.3%; diastolic: 16.5 ± 1.0%) than during the night (systolic: 9.1 ± 0.8%; diastolic: 10.8 ± 1.1%). The blood pressure load (percentage of values above 140/90 mmHg) during the night was significantly higher than during the day for both systolic (41.2 ± 8.1 vs. 19.6 ± 4.7%) and diastolic blood pressure (24.9 ± 6.9 vs. 16.3 ± 4.9%). There was a decrease in heart rate in both groups during the night. A fall of 25 mmHg or more in systolic blood pressure after meals occurred in ten patients with orthostatic hypotension and in one patient without orthostatic hypotension. These results indicate that orthostatic hypotension in Parkinson's disease is associated with specific modifications of ambulatory blood pressure including loss of circadian rhythm of blood pressure, increased diurnal blood pressure variability and post-prandial hypotension.     

Corneal D.C. recordings of slow ocular potential changes such as the ERG c-wave and the light peak in clinical work

A set-up for D.C. recordings of slow ocular potentials such as the c-wave of the electroretinogram (ERG) as well as the fast oscillation (FO), the light peak (LP) and the dark trough (DT) in both clinical and experimental work is described. It includes matched calomel half-cells connected by saline-agar bridges to a corneal contact lens on the eye and a reference chamber on the forehead, a low-drift differential-input D.C. amplifier, an A/D converter, a computer, a thermoprinter, a flexible disc memory, a plotter, and a device for light stimulation controlled by the computer.Examples of the usefulness of the set-up in clinical work are shown in the form of D.C. c-wave ERGs of normal subjects as well as of patients with vitelliform macular degeneration, choriocapillaris atrophy, and retinitis pigmentosa. The direct corneal recording of the FO and LP is demonstrated as well. The different origins of the standing potential (SP) of the eye, the ERG c-wave, the FO and the LP are reviewed briefly.     

A low-voltage activated,transient calcium current is responsible for the time-dependent depolarizing inward rectification of rat neocortical neurons in vitro

Intracellular recordings were obtained from rat neocortical neurons in vitro. The current-voltage-relationship of the neuronal membrane was investigated using current- and single-electrode-voltage-clamp techniques. Within the potential range up to 25 mV positive to the resting membrane potential (RMP: –75 to –80 mV) the steady state slope resistance increased with depolarization (i.e. steady state inward rectification in depolarizing direction). Replacement of extracellular NaCl with an equimolar amount of choline chloride resulted in the conversion of the steady state inward rectification to an outward rectification, suggesting the presence of a voltage-dependent, persistent sodium current which generated the steady state inward rectification of these neurons. Intracellularly injected outward current pulses with just subthreshold intensities elicited a transient depolarizing potential which invariably triggered the first action potential upon an increase in current strength. Single-electrode-voltage-clamp measurements reveled that this depolarizing potential was produced by a transient calcium current activated at membrane potentials 15–20 mV positive to the RMP and that this current was responsible for the time-dependent increase in the magnitude of the inward rectification in depolarizing direction in rat neocortical neurons. It may be that, together with the persistent sodium current, this calcium current regulates the excitability of these neurons via the adjustment of the action potential threshold.     

Whole-cell currents from the cloned canine cardiac Na+/Ca2+ exchanger NCX1 overexpressed in a fibroblast cell CCL39

 A conventional patch-clamp technique was used to record the whole-cell current from the cloned canine cardiac Na⁺/Ca²⁺ exchanger NCX1 overexpressed in a fibroblast cell. Ca²⁺ was extracellularly applied to the Na⁺-loaded cell to activate the outward current by operating the reverse mode of NCX1. No measurable outward current was ever elicited from the nontransfected cell. Na⁺/Ca²⁺ exchange blocker 5 mM Ni²⁺ or 3 μM KB-R7943 that was applied extracellularly abolished the outward current. With 140 mM external Li⁺ (replacing Na⁺), the outward current was transient during the Ca²⁺ application. In contrast, with 140 mM external Na⁺, the outward current was maintained without any inactivation during the Ca²⁺ application. I–V relations predicted from the whole-cell clamp protocols used were obtained both before and during the Ca²⁺ application. The exchanger whole-cell currents are thus successfully detectable from NCX1 which is overexpressed in this stable transfectant system. Received: 28 February 1997 / Accepted: 9 April 1997     

Hyperpolarization of hypothalamic parvocellular neurons by 17 β-estradiol and their identification through intracellular staining with procion yellow

Summary Intracellular recordings and injections of procion yellow (PY) were made in parvocellular neurons in hypothalamic slices of female guinea pigs. Eighty-five neurons, with an average resting membrane potential of -35 mV, were recorded in the arcuate (ARC) ventromedial (VM), and in the cellpoor zones between the ARC and VM. Eleven of the ARC neurons and four neurons from the cell-poor zone could be driven antidromically by median eminence (ME) stimulation, nine other neurons from the three areas could be driven orthodromically by stria terminalis (ST) stimulation.Twenty-eight parvocellular neurons were tested with 17 -estradiol (E₂), which was applied in the bathing medium as the free steroid. Eleven neurons (nine ARC and two cell-poor-zone neurons) were hyperpolarized 2 to 24 mV by 10^–10 M E₂ concentrations. 10^–8 M estrone concentration was without effect on three of these cells. Through the intracellular injection of PY, the estrogen-sensitive neurons (N = 11) were identified as small fusiform cells with few dendrites. Spine-like appendages were found on only one of these cells. None of the larger pyramidal-like neurons of these areas responded to the application of E₂.Postdoctoral research fellow of the National Institute of Neurological and Communicative Disorders and Stroke     

Relationship between saccadic eye movements and cortical activity as measured by fMRI: quantitative and qualitative aspects

We investigated the quantitative relationship between saccadic activity (as reflected in frequency of occurrence and amplitude of saccades) and blood oxygenation level dependent (BOLD) changes in the cerebral cortex using functional magnetic resonance imaging (fMRI). Furthermore, we investigated quantitative changes in cortical activity associated with qualitative changes in the saccade task for comparable levels of saccadic activity. All experiments required the simultaneous acquisition of eye movement and fMRI data. For this purpose we used a new high-resolution limbus-tracking technique for recording eye movements in the magnetic resonance tomograph. In the first two experimental series we varied both frequency and amplitude of saccade stimuli (target jumps). In the third series we varied task difficulty; subjects performed either pro-saccades or anti-saccades. The brain volume investigated comprised the frontal and supplementary eye fields, parietal as well as striate cortex, and the motion sensitive area of the parieto-occipital cortex. All these regions showed saccade-related BOLD responses. The responses in these regions were highly correlated with saccade frequency, indicating that repeated processing of saccades is integrated over time in the BOLD response. In contrast, there was no comparable BOLD change with variation of saccade amplitude. This finding speaks for a topological rather than activity-dependent coding of saccade amplitudes in most cortical regions. In the experiments comparing pro- vs anti-saccades we found higher BOLD activation in the "anti" task than in the "pro" task. A comparison of saccade parameters revealed that saccade frequency and cumulative amplitude were comparable between the two tasks, whereas reaction times were longer in the "anti" task than the pro task. The latter finding is taken to indicate a more demanding cortical processing in the "anti" task than the "pro" task, which could explain the observed difference in BOLD activation. We hold that a quantitative analysis of saccade parameters (especially saccade frequency and latency) is important for the interpretation of the BOLD changes observed with visual stimuli in fMRI.     

Methyldopa produces central inhibition of parasympathetic activity in the cat

Summary -Methyldopa (10–100 mg/kg i.v.) produced a dose-dependent pupillary dilation in anaesthetized cats which was antagonized by subsequent administration of yohimbine hydrochloride (0.5 mg/kg i.v.). The peak effects were observed approximately 2–3h after injection. This -methyldopa-induced mydriasis was present only when the parasympathetic innervation to the iris was intact. Prior treatment with yohimbine (0.5 mg/kg i.v.) 30 min before -methyldopa also antagonized the mydriatic effect, whereas pretreatment with phenoxybenzamine (2.5 mg/kg i.v.) did not. In contrast, phenoxybenzamine, but not yohimbine, effectively antagonized the pupillary dilation produced by adrenaline (0.3–10.0 g/kg i.v.). These results suggest that -methyldopa produces mydriasis in the cat by means of CNS inhibition of tonic outflow from the oculomotor nucleus and that an -adrenergic inhibitory mechanism may be involved. This conclusion is supported further by experiments in which direct measurements of ciliary nerve activity were made.     

Long-term Potentiation of NMDA Receptor-mediated EPSP in Guinea-pig Hippocampal Slices

Hippocampal slices from guinea-pigs were used to examine the long-term potentiation (LTP) of the N-methyl-d-aspartate (NMDA)-mediated excitatory postsynaptic potential (EPSP). Intracellular recordings were performed from CA1 pyramidal neurons in the presence of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 5 - 10 microM) and picrotoxin (50 microM). In these experimental conditions test stimuli applied at low frequency (0.1 Hz) to the Schaffer collateral - commissural pathway evoked a prolonged EPSP (150 - 200 ms). To obtain this CNQX-resistant EPSP, stimulus intensities had to be raised above the level required to evoke an EPSP of comparable amplitude in physiological solution. Tetanic stimulation (two trains of 100 Hz, 1 s every 20 s) led to a potentiation of the CNQX-resistant EPSP, and this potentiated response was abolished with d-(-)-2-amino-5-phosphonovaleric acid (50 microM). The potentiation of the NMDA receptor-mediated EPSP was more pronounced for strong than for weak test stimuli, and was suppressed when test EPSPs were evoked during membrane hyperpolarization. These results suggest that NMDA receptor-mediated responses can undergo LTP, and hence can contribute to the maintenance of LTP.