Search PubMed⌕ Search

Biomedical subjects

C Nicholson

Publications and source records attributed to C Nicholson.

At least 37 records · Page 2Linked to original sources
PubMed1988

Diffusion of penicillin in agar and cerebral cortex of the rat.

The diffusion of penicillin was studied in agar gel and the cerebral cortex of the rat using pressure microinjection and ion-selective microelectrodes selective to penicillin. From the agar measurements a free diffusion coefficient for penicillin of 3.52 +/- 0.08 (mean +/- S.E.M.) X 10(-6) cm2.s-1 for 37 degrees C was determined. The tortuosity value in the cortex was 1.62 +/- 0.03 (mean +/- S.E.M.) at the same temperature implying an apparent diffusion coefficient of 1.34 +/- 0.07 (mean +/- S.E.M.) x 10(-6) cm2.s-1. This tortuosity value means that penicillin diffuses in the cortex in a similar manner to other extracellular substances. These diffusion values clarify previous estimates and permit accurate evaluation of epilepsy models based on the application of penicillin.

Agar↗
PubMed1988

Magnetic field associated with spreading depression: a model for the detection of migraine.

Slow variations of the magnetic field were recorded in real time during spreading depression (SD) in the isolated turtle cerebellum. The magnetic signal lasted for 2-10 min with the largest amplitude in the first minute. The field strength was of sufficient magnitude to be measured unaveraged at 2-4 cm from the tissue. The directions and time course of the magnetic signal indicated that cerebellar SD is accompanied by current normal to the cerebellar surface. The observations reported here are of clinical interest due to the potential involvement of SD in various neurological disorders, notably head trauma and migraine.

Animals↗
PubMed1988

Magnetic evoked field associated with transcortical currents in turtle cerebellum.

The neural basis of magnetic evoked fields of the brain was studied with an isolated turtle cerebellum as a model preparation. The turtle cerebellum is a nearly flat tissue with neural processes arranged along three orthogonal axes of symmetry. According to theoretical results, this geometry should enable us to selectively measure the magnetic field due to a subpopulation of nerve cells whose longitudinal axes are perpendicular to the cerebellar surface, by simply placing the cerebellum vertically in the bath so that these cells are horizontal and by measuring the field along the rostrocaudal axis perpendicular to the longitudinal axis of these nerve cells. To elicit neural activity in these cells the dorsal midline was electrically stimulated with a bipolar electrode. Consistent with our expectations, the one-dimensional profile of the field normal to bath surface (Bz) was antisymmetrical along the rostrocaudal axis, implying that the underlying currents were transcortical. Also, the Bz field at a field extremum varied as a cosine of the orientation of the cerebellum when it was rotated about its rostrocaudal axis with the amplitude being zero when the cerebellum was horizontal. The Bz field was dipolar as judged by statistically excellent fits of the dipolar field to the one-dimensional field profile and to the distance function relating the field magnitude at an extremum to measuring distance. This was the case even for the initial component thought to be due to antidromic action currents invading the soma and dendrites of Purkinje cells. We also showed that the dipolar term of the source could be localized within 1 mm of the actual source location in most cases.

Animals↗
PubMed1988

Magnetic localization of neuronal activity in the human brain.

The performance of a cryogenic system that monitors the extracranial magnetic field simultaneously at 14 positions over the scalp has been evaluated to determine the accuracy with which neuronal activity can be located within the human brain. Initially, measurements were implemented on two model systems, a lucite sphere filled with saline and a model skull. With a magnetic field strength similar to that of a human brain, the measurement and analysis procedures demonstrated a position accuracy better than 3 mm, for a current dipole 3 cm beneath the surface. Subsequently, measurements of the magnetic field pattern appearing 100 ms after the onset of an auditory tone-burst stimulus were obtained in three human subjects. The location of the current dipole representing intracellular ionic current in active neurons of the brain was determined, with 3-mm accuracy, to be within the cortex forming the floor of the Sylvian fissure of the individual subjects, corresponding closely to the Heschl gyrus as determined from magnetic resonance images. With the sensors placed at appropriate positions, the locations of neuronal sources for different tone frequencies could be obtained without moving the recording instrument. Adaptation of activity in human auditory cortex was shown to reveal long-term features with a paradigm that compared response amplitudes for three tones randomly presented.

Brain↗
PubMed1988

Effects of electric fields on transmembrane potential and excitability of turtle cerebellar Purkinje cells in vitro.

1. Transmembrane potential (TMP) responses of Purkinje cells (PCs) in isolated turtle cerebellum to externally applied quasi-steady-state electric fields aligned with the dendritic axis were continuously measured using simultaneous intracellular and extracellular recording. TMP was obtained by subtraction of extracellular voltage fields from intracellular potential recorded at the same depth in the cerebellum. 2. The applied field changed the TMP with the polarity and amplitude dependent on the location on the PC membrane. This response at a given location increased linearly with external field up to a threshold level, beyond which active responses appeared. 3. The basic effect on TMP consisted of depolarization in the half of the dendrite towards which the fields were directed, and hyperpolarization in the other half. A pooled TMP depth-profile shows a steady increase in polarization from the middle of the molecular layer towards each end. This profile correlates with that predicted from previously proposed cable models, giving them empirical support for the first time. 4. Active responses were triggered by the field-induced depolarization. Tetrodotoxin (TTX)-sensitive action potentials arose with the primary depolarization in the somatic region. Notched, Ca2+-dependent action potentials arose with primary depolarization in the distal and mid-dendritic regions. 5. A TTX-sensitive voltage plateau was triggered by TMP-depolarization in the proximal region. It in turn activated Na+-spike trains. The frequency of spiking was proportional to the external field. At around 160 spikes/s, the Na+ spikes inactivated, and the TMP level rose to a more depolarized plateau. This latter plateau was also TTX-sensitive. 6. During depolarization of the distal dendritic region, sometimes a Ca2+-dependent plateau was observed. It appears to be associated with a small conductance increase. 7. Field-induced hyperpolarization suppressed local spiking and voltage plateaux, but remote Ca2+ spikes with reduced amplitude appeared in recordings from the proximal region. Similarly, in the distal region, low-amplitude, remote Na+ spikes and a Na+ plateau were observed superimposed on the hyperpolarizing baseline. The Na+ plateau apparently did not contribute to shunting of membrane currents in the distal dendrite. 8. The phase characteristics of the action potentials correlate with the modulation pattern noted in our extracellular study (Chan & Nicholson, 1986). Thus, the extracellular units ("giant spikes") were probably Na+ spikes activated in the soma and spread distally. Occasionally Ca2+ spikes, with a higher threshold, might also be activated to give dual-phase response.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1985

Organization of the filum terminale in the frog.

The histological organization of the filum terminale of the spinal cord in Rana catesbeiana and Rana pipiens was characterized to determine if this region possessed an organized neuropil or whether it was merely a glial remnant that persisted after absorption of the larval tail. The excised filum was maintained in vitro. Intracellular electrophysiological recording was performed with horseradish peroxidase injection. Tyrosine hydroxylase and serotonin distribution were revealed by immunocytochemical methods. Astroglia were the dominant cell type and displayed an elaborate variety of forms. The mean membrane potential was logarithmically related to the extracellular potassium concentration but displayed a sub-Nernstian slope. Oligodendroglia were also seen, as well as ependyma that extended from the central canal to the pial surface. Neuronal activity was revealed by occasional intracellular penetration of elements that displayed spontaneous excitatory postsynaptic or action potentials. The major evidence for the presence of neurons was the demonstration of tyrosine hydroxylase (TH) immunoreactivity in a large population of cerebrospinal fluid-contacting neurons that abutted the ventral half of the central canal. The axons of these cells entered a ventral bundle and ascended the cord; some fibers left this tract and apparently terminated on large arcuate neurons within the filum. Serotoninergic fibers were primarily confined to a subpial location at the dorsal midline. We conclude that the filum terminale of the frog has a sparse but functional neuropil that is organized around the central canal and supported by a profusion of elaborate glial forms.

Animals↗
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↗