PubMed Health⌕ Search

Biomedical subjects

C J Wilson

Publications and source records attributed to C J Wilson.

At least 19 recordsLinked to original sources
PubMed1992

Dopamine receptor subtypes colocalize in rat striatonigral neurons.

Dopaminergic neurons of the substantia nigra provide one of the major neuromodulatory inputs to the neostriatum. Recent in situ hybridization experiments have suggested that postsynaptic dopamine receptors are segregated in striatonigral and striatopallidal neurons. We have tested this hypothesis in acutely isolated, retrogradely labeled striatonigral neurons by examining the neuromodulatory effects of selective dopaminergic agonists on Na currents and by probing single-cell antisense RNA populations with dopamine receptor cDNAs. In most of the neurons examined (20/31), the application of the D1 dopamine receptor agonist SKF 38393 reduced evoked whole-cell Na+ current. The D2 agonists quinpirole and bromocriptine had mixed effects; in most neurons (23/42), whole-cell Na+ currents were reduced, but in others (8/42), currents were increased. In cell-attached patch recordings, bath application of SKF 38393 decreased currents as in whole-cell recordings, whereas quinpirole consistently (6/10) enhanced currents--suggesting that D2-like receptors could act through membrane delimited and non-delimited pathways. Changes in evoked current were produced by modulation of peak conductance and modest shifts in the voltage dependence of steady-state inactivation. Antisense RNA probes of dopamine receptor cDNA Southern blots consistently (5/5) revealed the presence of D1, D2, and D3 receptor mRNA in single striatonigral neurons. These findings argue that, contrary to a strict receptor segregation hypothesis, many striatonigral neurons colocalize functional D1, D2, and D3 receptors.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1992

Grafted neostriatal neurons express a late-developing transient potassium current.

Previous anatomical and physiological studies of neostriatal grafts have suggested that transplanted neurons do not develop beyond an early postnatal stage. We have tested whether this hypothesis can be generalized by characterizing the developmentally regulated Ca-independent potassium currents in graft neurons. These currents were studied using a combination of the whole-cell voltage-clamp technique with acutely-dissociated neurons and intracellular recording in slices. In all of the graft neurons examined with voltage-clamp techniques (n = 13), evidence was found for a slowly-inactivating potassium current that is seen only beyond the third or fourth postnatal week in normal rats. A current resembling the delayed rectifier was also seen in all sample neurons. The rapidly inactivating A-current which dominates recordings from nearly all immature neurons was seen in only about half (54%, 7/13) of the graft neurons; in a sample of normal adult striatal neurons, the A-current was detected in a similar percentage of neurons (41%, 25/62). Recordings of graft neurons in slices corroborated the voltage-clamp findings in revealing a slowly inactivating outward current that acts in the subthreshold potential range. These findings suggest that graft neurons express the normal complement of depolarization-activated potassium channel proteins seen in adult neurons.

Animals↗
PubMed1992

Morphology of intracellularly stained spiny neurons in rat striatal grafts.

Two to six months after implantation of fetal striatal primordia into the kainic acid-lesioned neostriatum of adult rats, spiny neurons in the grafts were stained intracellularly with biocytin. To determine whether the spiny neurons in the grafts differentiate morphologically as in the host neostriatum, the intracellularly stained spiny neurons in the grafts were studied with light and electron microscopy and compared with that of spiny neurons in the host neostriatum. The spiny neurons in the grafts had ovoid or polygonal cell bodies with dendrites radiating in all directions. The somata were smooth and the dendrites, except for their most proximal portions, were rich in spines. All these features resembled the appearance of spiny neurons in the intact neostriatum. However, quantitative studies showed that the somata of spiny neurons in the grafts were larger than those in the host neostriatum (projected cross-sectional areas of 230 +/- 64.6 microns 2 in the grafts and 158 +/- 28.9 microns 2 in the host) and the spine density of graft neurons was lower than that of host neurons. Cells near the border of the grafts had dendrites extending both into the graft and into the host neostriatum. In these cells, the dendrites in the grafts had fewer spines than the dendrites in the host tissue. The axons of spiny neurons in the grafts had very large and dense intrastriatal collateral arborizations, which occupied a much larger volume than that of the dendritic domain of the parent cells. The local axonal arborizations of each of these cells filled almost the entire graft. In some cells, axonal branches were traced outside the grafts and were seen to enter the internal capsule fascicles. Unlike spiny neurons in the normal adult neostriatum, the spiny cells of the graft could have nuclear indentations. With this exception, the ultrastructural features of spiny neurons in the grafts were very similar to those in the hosts. Many unlabeled boutons made synapses on identified spiny neurons in the grafts. Terminals with small round vesicles made synaptic contacts on dendritic shafts and dendritic spines, while terminals with flattened or pleomorphic vesicles contacted somata, dendrites, and dendritic spines. Labeled axon collaterals of graft neurons made symmetrical synapses on somata, dendrites and spines in the grafts and in the host neostriatum. In the grafts, more than 60% of the axon terminals contacted dendritic shafts. The proportion of axosomatic and axospinous synapses varied substantially from cell to cell.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

The relationship between attitude to disabled siblings and ratings of behavioural competency.

The impact of maturation factors and functioning level on the relationship between disabled and non-disabled siblings was examined. Two groups of adults, distinguished by level of functioning of their mentally retarded sibling, completed a Schaefer Sibling Behavior Inventory (SBI) and participated in a semi-structured interview. The latter explored a number of dimensions of the relationship including degree of warmth, contact and involvement. Judgements about involvement and comfort as remembered from the past and judgements about the present were obtained to derive hypotheses about possible changes with time. Data from the SBI indicated that significantly more competent siblings tended to be involved in relationships with a higher degree of reciprocity. In contrast, measures of attitude derived from interview data did not appear to relate to the functioning level of the sibling in any systematic manner. The results suggest that level of discomfort with peers may decrease significantly over the years with neither level of functioning nor gender being important variables. The extent to which non-disabled individuals expressed a preparedness to participate in the life of their disabled sibling may relate to the life-stage of the two. Males in particular anticipated increased future involvement. Although higher-functioning siblings were described as more active in the relationship, this did not appear to influence perceived positiveness of regard. The implications of these results are discussed briefly.

Activities of Daily Living↗
PubMed1991

Restoration of thalamostriatal projections in rat neostriatal grafts: an electron microscopic analysis.

The thalamostriatal projections to rat neostriatal grafts were studied by using the Phaseolus vulgaris-leucoagglutinin (PHA-L) axonal tracing technique. Two to 6 months after implantation of striatal primordia into adult neostriata, PHA-L was injected into two different portions of the intralaminar nuclear complex of the thalamus. In the host neostriatum, labeled fibers from the parafascicular nucleus (PF) arborized in a large region in the neostriatum, but avoided small patchlike areas. Most of the fibers from PF had irregular curved trajectories with short side branches that formed boutons. Labeled fibers from the centromedial and paracentral nuclei (CeM-PC) projected to a similarly large area within the neostriatum but did not show any nonuniformity. CeM-PC axons had relatively straight trajectories and formed boutons en passant. Both sets of thalamostriatal projection fibers were found in the grafts. Some of the labeled fibers in the grafts formed dense, focal arborizations. Compared to the host neostriatum, the distribution of postsynaptic elements in the grafts was altered dramatically. In the host neostriatum, 89% of the terminals from PF terminated onto dendritic shafts; 93% of the CeM-PC terminals contacted dendritic spines. However, only 47% of the PF terminals in the grafts contacted dendritic shafts; 53% of them terminated on dendritic spines. In grafts, 81% of the terminals from CeM-PC region contacted dendritic spines; 19% of them made synapses on dendritic shafts. The shift of postsynaptic elements in the grafts suggests a loss of pathway specificity in the induction of dendritic spines on neostriatal neurons in grafts.

Animals↗
PubMed1991

Synaptic potentials evoked in spiny neurons in rat neostriatal grafts by cortical and thalamic stimulation.

1. Fetal rat striatal primordia were implanted into the neostriatum of adult rats 2 days after kainic acid lesion. Two to 6 mo after transplantation, in vivo intracellular recording and staining were performed to study the responses of spiny neurons in the grafts to the cortical and thalamic stimuli. The physiological characteristics and synaptic responses of 27 cells recorded in the grafts were compared with a sample of 23 neurons recorded from the surrounding host neostriatum in the same animals. Nineteen of the graft neurons and 19 of the host neurons were identified as spiny neurons by intracellular staining with biocytin. The responses of the remaining neurons were the same as those of identified spiny cells. 2. The spontaneous synaptically driven membrane potential shifts and long-lasting responses to afferent stimulation that are characteristic of neostriatal cells in normal animals were greatly reduced or absent in graft neurons. Presumably this reflects the reduction in synaptic input to the grafts and the lack of convergence of inputs from diverse sources. 3. Short-latency synaptic responses to cortical and thalamic stimulation were present and could consist of either excitatory postsynaptic potentials (EPSPs) or inhibitory postsynaptic potentials (IPSPs). The IPSPs were accompanied by a membrane conductance increase, and their reversal potentials could be altered by injection of chloride ions. Several minutes after impaling the cell, the IPSPs gradually disappeared, and the same stimuli could then evoke EPSPs. The disappearance of the IPSPs was independent of the presence of chloride in the electrodes. Most of the EPSP responses appeared to be monosynaptic but occurred at longer latencies than those seen in host neurons of the same type. 4. In cells not exhibiting IPSPs, or after the IPSP responses disappeared, cortical or thalamic stimulation could evoke slow depolarizing potentials and bursts of action potentials. These could not be evoked by current injection. They could be prevented or delayed by an exaggerated action potential after hyperpolarization that developed in neurons maintained in a depolarized state for several seconds, but could not be prevented by passage of hyperpolarizing current from the recording electrode. 5. The input resistance of graft spiny neurons was higher than that of the host cells, and time constants were longer. Both of these properties appeared to be due to the absence of the strong inward rectification that is usually present at resting membrane potentials in neostriatal neurons.

Animals↗
PubMed1991

Correlation of physiologically and morphologically identified neuronal types in human association cortex in vitro.

1. We examined whether the three physiologically defined neuron types described for rodent neocortex were also evident in human association cortex studied in an in vitro brain slice preparation. We also examined the relationship between physiological and morphological cell type in human neocortical neurons. In particular, we tested whether burst-firing neurons were numerous in regions of human cortex that are susceptible to seizures. 2. Although we sampled regular-spiking and fast-spiking neurons, we observed no true burst-firing neurons, as defined for rodent cortex. We did find neurons that displayed a voltage-dependent shift in firing behavior. Because this behavior was due, in large part, to a low-threshold calcium conductance, we called these cells low-threshold spike (LTS) neurons. 3. Regular-spiking neurons and LTS neurons only differed in the voltage dependence of firing behavior and the first few interspike intervals (ISIs) of repetitive firing in response to small current injections (from hyperpolarized membrane potentials). Because of the general similarities between the two types, we consider the LTS cells to be a subgroup of regular-spiking cells. 4. All biocytin-filled regular-spiking neurons were spiny and pyramidal and found in layers II-VI. The lone filled fast-spiking cell was aspiny and nonpyramidal (layer V). The LTS neurons were morphologically heterogeneous. We found 80% of LTS neurons to be spiny and pyramidal, but 20% were aspiny nonpyramidal cells. LTS neurons were located in layers II-VI. 5. In conclusion, human association cortex contains two of three physiological cell types described in rodent cortex: regular spiking and fast spiking. These physiological types corresponded to spiny, pyramidal, and aspiny, nonpyramidal cells, respectively. We sampled no intrinsic burst-firing neurons in human association cortex. LTS neurons exhibited voltage-dependent changes in firing behavior and were morphologically heterogeneous: most LTS cells were spiny and pyramidal, but two cells were found to be aspiny and nonpyramidal. It is not clear whether the absence of burst-firing neurons or the morphological heterogeneity of LTS neurons are due to species differences or differences in cortical areas.

Association Learning↗
PubMed1991

The Periotest method for determining implant success.

The purpose of this paper is to show that the currently accepted methods for the determination of implant stability are unpredictable. It describes those techniques that are currently utilized for the assessment of implant success and discusses the problems they present. The paper will propose the Periotest method as a reliable and reproducible alternative to the methods currently available to the clinician for determining implant stability.

Dental Implants↗
PubMed1990

Parvalbumin-containing GABAergic interneurons in the rat neostriatum.

Antibodies to the intracellular calcium binding protein parvalbumin were shown to label specifically a distinct group of neostriatal GABAergic neurons. These neurons corresponded to the intensely staining subclass of neostriatal GABAergic neurons that have previously been shown to be a class of aspiny interneurons in the neostriatum. The parvalbumin neurons were aspiny neurons with varicose dendrites distributed throughout the neostriatum in a pattern identical to the intensely stained GABA neurons, and both populations of neurons showed increased numbers in the lateral part of the neostriatum. Double labeling of single neurons with both the GABA and parvalbumin antisera showed that all parvalbumin neurons were positive for GABA, but some GABA labelled neurons were not immunoreactive for parvalbumin. These parvalbumin-negative GABAergic neurons were morphologically similar to the spiny projection neurons, which are GABAergic but usually are not so heavily stained. The relationship of the GABA-containing parvalbumin neurons to the striatal mosaic organization was determined by using immunocytochemistry for another calcium binding protein, calbindin D28K, to label the matrix compartment of the striatum. The distribution of parvalbumin-positive neurons relative to the calbindin-positive matrix and calbindin-poor patches was determined by using pairs of adjacent sections stained with the calbindin and parvalbumin antisera. This analysis showed that the somata of the parvalbumin neurons were present in both patch and matrix compartments, and their axons and dendrites crossed the boundaries between compartments. A quantitative analysis of the number of neurons in each compartment revealed that the neurons showed no preferential distribution in either compartment, but instead were present according to the area occupied by that compartment.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Interaction of cimetidine with human serum albumin.

Ultrafiltration studies have detected the existence of a weak interaction between cimetidine and human serum albumin, a finding supported by corresponding studies with this xenobiotic and bovine serum albumin. Furthermore, the binding characteristics of the interaction with human serum albumin (4 sites, K = 630 M-1) more than suffice to account for the proportion of protein-bound drug in the serum of patients subjected to cimetidine therapy. Thus, although alpha 1-acid glycoprotein is usually regarded as the specific transporter of basic drugs, the present evidence implicates albumin as the likely binding protein for cimetidine in serum.

Binding Sites↗
PubMed1990

The use of a retroviral vector to identify foetal striatal neurones transplanted into the adult striatum.

A retrovirus which encodes beta-galactosidase was used to infect embryonic rat striatal cells before grafting these cells into the lesioned adult rat striatum. Examination of the grafts after long term survival (8 months) revealed that a few small and large cells expressed large amounts of bacterial beta-galactosidase activity. The larger diameter cells were identified as neurones by their size, shape and presence of neuronal processes. The identity of the small diameter cell types was not established.

Animals↗
PubMed1990

Projection subtypes of rat neostriatal matrix cells revealed by intracellular injection of biocytin.

Individual neostriatal-matrix spiny neurons were stained intracellularly with biocytin after intracellular recording in vivo, and their axons were traced into the globus pallidus (GP), entopeduncular nucleus (EP), and/or substantia nigra (SN). The locations of the neurons within the matrix compartment of the neostriatum (NS) were established by immunocytochemical counterstaining of sections containing the cell bodies using antibodies for calbindin-D28K. This allowed nearly complete visualization of the axonal projections of single NS neurons. On the basis of their intrastriatal axonal arborizations, matrix spiny neurons could be divided into 2 types. One type, which was the more common, had local axonal arborizations restricted to the region of the dendritic field, often with axon collaterals arborizing within the dendritic field of the cells of origin. A second, less common, cell type in the matrix had local axon collaterals distributed widely in the NS. Among matrix neurons with restricted local collateral fields, 3 subtypes could be distinguished on the basis of their efferent axonal projections. Type I cells projected only to the GP. Type IIa cells projected to the GP, EP, and SN pars reticulata. Type IIb cells projected to the GP and SN but not to the EP. The shapes and densities of the GP arborizations varied in the 3 cell types, with the cells projecting only to the GP (type I) projecting more heavily and filling a larger volume there than type II cells. The dendrites and intrastriatal axon collaterals of 3 subtypes were similar in morphology. The class of matrix spiny neurons with intrastriatal axon collaterals distributed widely in the NS were observed to project to the GP. Projections beyond the GP were not identified for this cell type, but could not be ruled out. Somatodendritic morphologies of neurons did not differ according to the projection site. These results demonstrate that NS matrix spiny cells are more heterogeneous in their efferent projection patterns than previously suspected on the basis of retrograde axonal tracing and immunocytochemical studies. As predicted by those previous studies, there is a class of matrix neurons that projects only to the GP. Presumably, these cells contain enkephalin. Cells projecting to the SN and EP, and so presumably containing substance P, give off a small projection to the GP, as well, and differ in their collateralization patterns within the 3 major target nuclei.

Animals↗
PubMed1990

Firing patterns and synaptic potentials of identified giant aspiny interneurons in the rat neostriatum.

Intracellular recordings were made in vivo from 9 giant aspiny neurons in the neostriatum of urethane-anesthetized rats. The cells were identified by intracellular staining with HRP or biocytin. The neurons exhibited morphological features typical of neostriatal cholinergic interneurons. Six of the cells were obtained from intact animals, while 3 were recorded from rats with ipsilateral hemidecortications. Giant aspiny neurons were characterized by their slow irregular but tonic (3-10/sec) spontaneous activity and long-duration action potentials. Examination of the underlying membrane potential trajectories during spontaneous firing revealed that individual action potentials were triggered from spontaneous small (1-5 mV) depolarizing potentials. These spontaneous potentials exhibited the voltage sensitivity of ordinary EPSPs. They were much less frequent during the 80-200 msec pause in tonic afferent input that follows the excitation evoked by cortical or thalamic stimulation, and were decreased in frequency in decorticate animals. Their rise times and half-widths matched those expected for unitary synaptic potentials placed proximally on the surface of the neurons. Low-intensity stimulation of neostriatal afferents produced small short-latency EPSPs that appeared to be composed of responses identical to the spontaneous depolarizing potentials. The latencies of the EPSPs evoked from the cerebral cortex and thalamus were consistent with a monosynaptic input from both structures, but the maximal size of the EPSPs was much smaller than that evoked in spiny neurons, suggesting that a smaller number of afferent inputs make synapses with each of the aspiny cells. Giant aspiny neurons exhibited much larger input resistances and longer time constants than spiny neostriatal neurons. They also exhibited relatively linear steady-state current-voltage relationship compared to spiny projection cells. Input resistances ranged from 71-105 M omega, and time constants ranged from 17.8-28.5 msec. Analysis of the charging transients in response to current pulses yielded estimates of dendritic length of approximately 1 length constant. Repetitive firing of the neurons was limited by a powerful spike afterhyperpolarization and by a strong spike frequency adaptation. The sensitivity of the giant aspiny interneuron to a relatively small number of proximal afferent synaptic contacts, its tonic firing, and its widespread dendritic and axonal fields place it in an excellent position to act as a modulator of the excitability of neostriatal projection neurons in advance of the onset of movement-related neostriatal activity.

Action Potentials↗
PubMed1989

Capacitance compensation and bridge balance adjustment in intracellular recording from dendritic neurons.

Under most experimental conditions in intracellular recording, the proper adjustment of the amplifier is essential for the interpretation of the signals recorded from neurons. It is considered possible to accurately align the capacitance compensation and bridge balance adjustments of the amplifier simultaneously with the recording of membrane potential of an impaled cell if a number of conditions are met. In the strictest sense, these conditions are met only if: (1) the neuron is isopotential and if its electrical behavior can be adequately described using a single exponential decay constant, and if (2) that decay time constant is much longer than that of the microelectrode. These conditions cannot usually be satisfied. Because intracellular adjustment of capacitance compensation and bridge balance is necessary in many circumstances, it is desirable, to know whether any of the methods for performing these adjustments are accurate when used under less strict constraints, and to assess the nature and degree of the error that can be expected when the constraints are ignored. The results of computer simulations of a simple intracellular recording amplifier, microelectrode and a dendritic neuron model consisting of an isopotential cell and terminated finite equivalent cylinder representation of the dendrites are presented here. These studies show that the introduction of fast components of the response to intracellular current transients by the redistribution of applied charge in dendrite neurons may sometimes make it impossible to correctly apply the conventional methods of capacitance compensation and bridge balance. If the high-frequency response of the intracellular recording amplifier has sufficient fidelity, however, these adjustments can be made to a sufficient degree of accuracy using the response to sine wave calibration signals of varying frequency.

Computer Simulation↗
PubMed1989

Restoration of the corticostriatal projection in rat neostriatal grafts: electron microscopic analysis.

The corticostriatal projection in rat neostriatal grafts was studied by using the axonal transport of Phaseolus vulgaris-leucoagglutinin. The neostriatal primodia from 15-18-day embryos were used to make a cell suspension which was implanted unilaterally into the rat neostriatum 3-5 days after kainic acid lesion. Two to four months later, regions of the frontal cortex ipsilateral to the grafts were injected iontophoretically with Phaseolus vulgaris-leucoagglutinin. There were many Phaseolus vulgaris-leucoagglutinin labeled cortical fibers in the host neostriatum. Although the density of labeled fibers in the grafts was much lower than that in the surrounding host tissue, some fibers could be seen to enter the grafts and form terminal arborizations. The morphology of labeled fibers in the graft differed from that of corticostriatal fibers from the same injection but distributing in the host neostriatum. The labeled fibers in the host neostriatum arborized in an extended pattern, branching infrequently and making most of their synapses en passant at varicosities along their courses. The labeled fibers in the grafts made more dense arborizations with many short branches that formed clusters of terminals confined to small foci along their courses. The cellular composition and the structure of the neuropil in the neostriatal grafts were similar to that of the neostriatum. As those in the host, labeled corticostriatal terminals in the grafts contained densely packed round vesicles and made asymmetric synapses on dendritic spines, dendritic shafts and somata. A quantitative analysis, however, revealed that the distribution of postsynaptic elements of labeled boutons in the grafts was different from that in the hosts. More than 90% of the labeled cortical terminals in the host neostriatum contacted dendritic spines whereas only 47% of the labeled terminals in the grafts contacted spines, and 50% of them terminated on the dendritic shafts. The present study provides direct anatomic evidence to demonstrate the restoration of the corticostriatal projection in grafts. The difference in the distribution of postsynaptic elements in the grafts and the hosts may represent a response to the decreased innervation density of cortical inputs to the graft tissue, and may contribute to the recovery of corticostriatal responses by increasing the effectiveness of transmission by the fibers that do grow into the graft and form contacts there.

Animals↗