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Biomedical subjects

C Nicholson

Publications and source records attributed to C Nicholson.

At least 55 records · Page 3Linked to original sources
PubMed1978

Calcium and potassium changes in extracellular microenvironment of cat cerebellar cortex.

1. Local stimulus-evoked changes in concentration of extracellular calcium ions, [Ca2+]0, and potassium ions, [K+[0, were measured in the cerebellar cortex of the cat using paired ion-selected micropipettes. 2. Repetitive stimulation of 30 s duration decreased [Ca2+]0 from a base line of 1.2 mM to as low as 0.8 mM and increased [K+]0 from 3 mM to as much as 8 mM. The magnitude of the changes was directly related to stimulus frequency. Laminar analysis showed that the greatest ion changes occurred at the level of maximum parallel fiber-Purkinje cell dendrite stimulation, but that the [Ca2+]0 changes were more localized than the [K+]0 changes. 3. Combining real-time current-source density measurement with [K+]0 determination and local manganese application, showed that the Mn blocked parallel fiber-Purkinje cell synaptic transmission, but that much of the [K+]0 changes persisted. Thus, a large part of the [K+]0 flux most probably originated in the parallel fibers. In contrast, [Ca2+]0 changes were abolished by the Mn, indicating that the decrease in this ion was probably associated with synaptic transmission or dendritic events. 4. In a few cases, spreading depression occurred in the cat cerebellar cortex. This could be accompanied by decreases in [Ca2+]0 to as low as 0.12 mM and increases in [K+]0 in excess of 48 mM. 5. These results show that significant changes in [Ca2+]0 and [K+]0 occur during cerebellar stimulation and indicate possible origins of the ion fluxes in terms of neuronal elements. This work also shows that the cerebellar cortex of the cat can support spreading depression. The present results, together with those of earlier studies on [Ca2+]0 and [K+]0 changes in the presence of aminopyridine in the cat cerebellum, suggest that synaptic or dendritic electroresponsive properties may play a role in the observed [Ca2+]0 and [K+]0 changes.

Animals↗
PubMed1977

Calcium modulation in brain extracellular microenvironment demonstrated with ion-selective micropipette.

Changes in extracellular Ca2+ concentration were directly measured in the rat cerebellum, using an ion-selective micropipette. Extracellular K+ was measured simultaneously with a second ion-selective micropipette. The potential reference barrels of the ion electrodes also provided fast field and slow potentials. During repetitive stimulation of the parallel fiber--Purkinje cell cerebellar circuit, extracellular Ca2+ fell to about 80% of base line concentration. During the spreading depression of Leão, extracellular Ca2+ fell to about 10% of base line; decreases of this magnitude also occurred during terminal anoxia. In all cases extracellular K+ increased substantially. These results show that extracellular Ca2+ is modulated during neuronal activity in the central nervous system and that under some conditions the Ca2+ change can be extreme. Given the well-established and antagonistic effects of reduce extracellular Ca2+ on axonal excitability and synaptic transmission, these results suggest that Ca2+ modulation in the brain cell microenvironment may be a significant parameter in the behavior of neuronal ensembles.

Animals↗
PubMed1976

Climbing fiber evoked potassium release in cat cerebellum.

K+-selective micropipettes were used to measure the extracellular K+-signal associated with the activation of a single Purkinje cell, via a climbing fiber (CF). The maximum K+-signal had a magnitude of 0.3 - 0.5 mM and was correlated with a positive all-or-none extracellular potential. The ionic signal was of the same order of magnitude as that evoked from a population of Purkinje cells by local stimulation of a parallel fiber beam. The large size of the CF-evoked K+-response supports the concept of dendritic spikes under these conditions and may be relevant to CF function.

Animals↗
PubMed1976

Reversal properties of climbing fiber potential in cat Purkinje cells: an example of a distributed synapse.

1. The electrophysiological properties of the EPSP generated in Purkinje cells by the activation of CFs were studies in the cat cerebellar cortex. 2. CF-EPSPs were evoked by electrical stimulation of the cerebellar white matter and recorded intracellularly from the soma of the Purkinje cells. 3. Current was injected into the Purkinje cells via the recording micropipette using a bridge amplifer in order to study the reversal properties of the EPSP. 4. The CF-EPSP reversal was biphasic with the early portion reversing first. 5. The reversed EPSP waveform was not a mirror image of the EPSP, but displayed a briefer time course. 6. A four-compartment computer stimulation showed that the reversal properities of the CF-EPSP were explicable in terms of a distributed synapse on a cable. 7. The biphasic reversal and asymmetry were shown to be due to the spatially nonuniform potential distribution created by the somatic current injection, which predominantly reversed the proximal part of the distributed synapse. Delayed rectification may also have contributed to the reversal asymmetry. 8. The advantages of a distributed synapse over a point synapse are discussed and the reversal properties of the CF-EPSP compared to those of the Ia-evoked EPSP in motoneurons.

Animals↗
PubMed1975

Calcium role in depolarization-secretion coupling: an aequorin study in squid giant synapse.

Aequorin, a protein that emits light in the presence of calcium, was injected in the presynaptic terminal of the squid giant synapse. This injection was preceded by intracellular tetraethylammonium administration, which prolonged the duration of the presynaptic action potential. After this procedure light emission was evoked by single presynaptic spikes capable of releasing synaptic transmitter. In a second set of experiments, presynaptic tetraethylammonium injection was followed by the administration of tetrodotoxin extracellularly, which abolished the presynaptic action potential. Under these conditions artificial depolarization of the presynaptic terminal triggered the release of synaptic transmitter, in a graded manner. However, as previously reported by other authors, membrane potential steps to an internal positive value of approximately plus 90 mV (the suppression potential) produced a blockage of transmitter release for the duration of the imposed potential. Synaptic transmission recurred, nevertheless, as the current injection was terminated. A similar set of experiments, performed after the intracellular injection of aequorin in the presynaptic fiber, demonstrated that the aequorin light response was evoked by membrane potential steps capable of releasing synaptic transmitter. If the membrane potential was made positive to the "suppression" level, no light response was evoked but the light emission appeared, as did transmitter release, at the end of the current pulse. These experiments demonstrate that release of transmitter is directly correlated with intracellular calcium concentration and that the suppression potential is compatible with the existence of a calcium equilibrium potential at the presynaptic terminal.

Action Potentials↗
PubMed1975

Theory of current source-density analysis and determination of conductivity tensor for anuran cerebellum.

The theoretical basis of current source-density (CSD) analysis in the central nervous system is described. Equations relating CSD, the current flow vector, and the extracellular field potential are given. It is shown that the CSD provides superior resolution of neuronal events when compared to conventional field-potential analysis. Expressions for the CSD in rectangular Cartesian coordinates are derived, including the general case of anisotropic, inhomogeneous conductive tissue, and a coordinate system rotated with respect to the principal axes (APPENDIX). The minimum number of spatial dimensions for accurate CSD analysis is discussed. The conductivity tensor was experimentally measured in frog and toad cerebella. All three principal components of the tensor were evaluated and their spatial gradients determined to be negligible. It was also shown that the conductivity was independent of potential. Thus the anuran cerebellum is anisotropic, homogeneous, and ohmic. On the basis of these results the appropriate mathematical expression for the CSD was selected.

Animals↗
PubMed1975

Experimental optimization of current source-density technique for anuran cerebellum.

This paper represents a systematic, semirigorous attempt to optimize the technique of current source-density (CSD) analysis experimentally. We compared different spatial differentiation formulas in terms of accuracy, aliasing, and smoothing, and provide experimental and theoretical rationale for their use. Sources of error have also been investigated. Expressions were derived to enable one to estimate the relative magnitude of errors due to electrical noise, uncertainty in tip position of recording electrodes, and error in the conductivity tensor. Corresponding experiments illlustrating the validity of such estimates are also presented. Methods to determine the optimum interelectrode spacing are given, based on computations of spatial energy-density spectra in the anuran cerebellum. The application of the technique of CSD analysis developed in this, and the accompanying paper, to the vestibulocerebellar input in the toad cerebellum provided significantly better temporal and spatial resolution of neuronal events than conventional field-potential analysis. Considerations germane to the optimum application of this technique to other neural structures are also discussed.

Animals↗