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Biomedical subjects

W F Collins

Publications and source records attributed to W F Collins.

At least 19 recordsLinked to original sources
PubMed1998

EPSP amplitude modulation at the rat Ia-alpha motoneuron synapse: effects of GABAB receptor agonists and antagonists.

The object of this study was to examine the relationship between excitatory postsynaptic potential (EPSP) amplitude, posttetanic potentiation, and EPSP amplitude modulation at synapses made by group Ia afferents on motoneurons in the rat. These relationships were evaluated in cells in untreated rats and in cells in rats treated with the gamma-aminobutyric acid-B (GABAB) receptor agonist baclofen and antagonist CGP-35348, which were used to manipulate Ca2+ entry into presynaptic terminals and consequently probability of transmitter release from them. There was no evidence for postsynaptic action of these drugs from measurement of their effects on motoneuron properties. During high-frequency stimulation (32 shock bursts at 167 Hz), EPSP amplitude either decreased (negative modulation) or increased (positive modulation) in response to successive stimuli at different connections. In untreated rats this frequency-dependent amplitude modulation behavior was inversely but weakly correlated with EPSP amplitude measured at low frequency. Intravenous (iv) administration of the GABAB agonist, baclofen, produced a marked and progressive decrease in EPSP amplitude measured at low frequency coincident with a change in frequency-dependent EPSP amplitude modulation toward more positive values (synaptic facilitation). In contrast, an increase in EPSP amplitude occurred after iv administration of the GABAB antagonist CGP-35348 that was accompanied by a negative shift in EPSP amplitude modulation during high-frequency stimulation. The negative shift in EPSP amplitude modulation (synaptic depression) after CGP-35348 application was much smaller than the positive shift induced by baclofen when normalized to the change in EPSP amplitude. Posttetanic potentiation decreased after baclofen but did not increase after CGP-35348. The relationship between modulation and EPSP amplitude was much steeper after GABAB receptor manipulation in either direction than that observed in the population of motoneurons in untreated preparations. This suggests that in the rat differences in probability of release play at most a small role in determining EPSP amplitude across the motoneuron pool.

Afferent Pathways↗
PubMed1997

Modulation of motoneuron excitability by brain-derived neurotrophic factor.

The influence of neurotrophins on motoneuron survival and development has been well documented in cell cultures and neonates. In the present study, the role of brain-derived neurotrophic factor (BDNF) in the maintenance of motoneuron electrical properties was investigated. In adult male rats, BDNF- or saline-saturated gelfoam was inserted between the medial and lateral heads of the gastrocnemius muscles. After 5 days survival, in vivo intracellular recordings were obtained, and motoneuron biophysical properties were measured. In BDNF-treated rats, significant decreases in mean rheobase and in total cell capacitance of medial gastrocnemius motoneurons were observed. In addition, a concommitant increase in input resistance and decrease in membrane time constant were noted in BDNF-treated rats but were not statistically significant. No significant treatment effect was observed in motoneuron conduction velocity, action potential amplitude, equalizing time constant, electrotonic length, afterhyperpolarization amplitude and duration, and membrane potential sag during current injection. The observed changes in motoneuron rheobase and total cell capacitance suggest that application of BDNF produces an increase in motoneuron excitability coincident with a reduction in size. These data are discussed with respect to the possible role of BDNF as a muscle-derived trophic factor for the regulation of motoneuron excitability.

Animals↗
PubMed1996

Yale neurosurgery program.

Organized neurosurgery at Yale began in 1918 with Dr. Sam Harvey. In 1928, Dr. William German became the first surgeon at Yale who was dedicated to neurosurgery. Both of these surgeons were trained by Harvey Cushing, and upon the arrival of Drs. Cushing and Eisenhardt in 1934, Yale developed a strong tradition in surgery of the nervous system. In 1967, Dr. William Collins established a training program for residents that integrated laboratory research and clinical experience. This tradition has continued under the guidance of Dr. Dennis Spencer since 1987. This article provides a brief overview of the history of neurosurgery at Yale, its current practice, and plans for the future.

Connecticut↗
PubMed1995

Differences in the connectivity of rat pudendal motor nuclei as revealed by retrograde transneuronal transport of wheat germ agglutinin.

Bilateral coordinated activation of pudendal motoneurons is an essential component of penile reflexes in male rats. However, little is known about the intraspinal organization of these reflexes. In the present study, retrograde transneuronal transport of wheat germ agglutinin (WGA) was used to examine the organization of spinal motoneurons and putative interneurons mediating penile reflexes in adult male rats. Injection of WGA into the ventral bulbospongiosus muscle resulted in direct retrograde labeling of motoneurons in the ipsilateral dorsomedial (DM) nucleus and transneuronal labeling of ipsilateral and contralateral DM motoneurons. Motoneurons in the ipsilateral and contralateral dorsolateral (DL) nuclei were not labeled. WGA-labeled putative interneurons were observed bilaterally, primarily in the ventromedial spinal gray matter extending dorsally to the central canal and the dorsal gray commissure. The number of transneuronally labeled putative interneurons increased with longer survival times. Injection of WGA into the ischiocavernosus muscle resulted in direct retrograde labeling of motoneurons in the medial subdivision of the ipsilateral DL nucleus. However, no WGA labeling was detected in motoneurons in the lateral subdivision of the ipsilateral DL nucleus, the contralateral DL nucleus, or the DM nuclei at any of the survival times studied (1-7 days). Only a small number of transneuronally labeled putative interneurons was observed in the ventrolateral gray matter at longer survival times (3-7 days). Thus, marked differences were observed between the DM and DL nuclei with respect to the transneuronal transport of WGA. These results are discussed with respect to the organization of the spinal circuits that mediate pudendal motor reflexes.

Animals↗
PubMed1995

Surgery in the acute treatment of spinal cord injury: a review of the past forty years.

This review is concerned with changes that have occurred during the past forty years in surgery as acute therapy for spinal cord injury. Included is a summary of experimental and clinical information upon which many of the decisions for change were based. Despite the evidence, following World War II, of improvement of mortality and morbidity with non-invasive treatment of spinal cord injuries, increased utilization of surgery has continued to the present. Reasons include a decrease in mortality and morbidity with modern surgical techniques, easier handling of the patient with an unstable spine who has early fusion, and the decrease in hospital and rehabilitation costs with earlier stabilization and earlier mobilization.

Activities of Daily Living↗
PubMed1994

Paraventriculospinal tract as a model for axon injury: spinal cord.

The response of immunocytochemically identified hypothalamic axons innervating the rat spinal cord was examined at varying times after cord hemisection in a model of axonal injury using the paraventriculospinal projection. The purpose was to determine whether these long descending peptidergic axons would show signs of regrowth after injury. From 1 to 180 days after hemisection, horizontal sections of the spinal cord were stained with peroxidase immunocytochemistry. Antiserum against neurophysin was used to identify axons projecting from the hypothalamic paraventricular nucleus to the spinal cord. The paraventricular nucleus innervates all rostrocaudal segments of the cord, yet the projection is not massive, allowing the trauma response of individual axons to be studied. Immediately caudal to a T4 hemisection, axons began decreasing in number by 2 days after surgery. Ten days postoperatively, only a few axons could be found caudal to the cut; these remaining axons arose from the contralateral cord. A substantial increase in the number of stained axons was found rostral to the hemisection 3-12 weeks after surgery. In that an increase in axon number could be due to both increasing staining efficacy and sprouting, the orientation of axons in control and hemisected rats was studied. Three millimeters rostral to the hemisection, axons had a greater variance in orientation and were more likely to project medially out of the dorsolateral white matter compared with the contralateral control side. Rostral to the hemisection, a statistically significant two- to fourfold increase in the number of branches per axons was found in comparison to the contralateral control side. Axons were found in the dorsal white matter 4 months after surgery; in controls, immunostained axons were not found here. At all intervals after surgery, structures suggestive of growth were found, including terminal growth cones and lateral filopodia and lamellipodia extending from axons whose distal ends had been severed by hemisection. Similar structures were not found in control spinal cord. Together, these data suggest that after cord hemisection, axons from the paraventricular nucleus sprout rostral to the injury.

Animals↗
PubMed1994

Retrograde determination of motoneuron properties and their synaptic input.

Both motoneurons and the muscle fibers that they innervate can vary widely in their properties. The finding that these properties are highly correlated indicates that these cells are not specified independently, but rather interact in some manner to achieve the observed coherence. The direction of the interaction, i.e., whether orthograde or retrograde, requires analysis beyond the simple observation of these correlated properties. Evidence, largely from experiments involving reinnervation of muscle by the original or a foreign motor nerve, suggests the action of retrogradely transported factors from the muscle as well as orthograde ones. Various possible factors, specifically neurotrophins, are advanced as possible candidates for retrograde specification. In addition, synaptic input to motoneurons also varies in a coordinated fashion in a manner that suggests a retrograde determination from the muscle. However, motoneuron properties and their synaptic input change after peripheral nerve manipulations such that they are no longer in register. This indicates some independence in retrograde specification of motoneurons and their synaptic input.

Animals↗
PubMed1994

The Journal of Neurosurgery in the computer era.

The fourth Editor of the Journal of Neurosurgery offers short vignettes on the Editors who preceded and succeeded him. He recounts some of the challenges that were faced and changes that were made during his time as Editor. One of the major changes was production of the Journal via computer.

Computers↗
PubMed1992

Differential effect of castration on the somal size of pudendal motoneurons in the adult male rat.

We have examined the organization of the androgen sensitivity of pudendal motoneurons in adult male rats. Comparisons of mean somal cross sectional area of pudendal motoneurons identified by retrograde labeling with horseradish peroxidase were made between three treatment groups: castrates with testosterone propionate supplementation, castrates with placebo, and sham castrates. Bulbospongiosus and ischiocavernosus motoneurons were sensitive to androgen treatment, whereas external anal sphincter and external urethral sphincter motoneurons were not.

Animals↗
PubMed1992

Methylprednisolone or naloxone treatment after acute spinal cord injury: 1-year follow-up data. Results of the second National Acute Spinal Cord Injury Study.

The 1-year follow-up data of a multicenter randomized controlled trial of methylprednisolone (30 mg/kg bolus and 5.4 mg/kg/hr for 23 hours) or naloxone (5.4 mg/kg bolus and 4.0 mg/kg/hr for 23 hours) treatment for acute spinal cord injury are reported and compared with placebo results. In patients treated with methylprednisolone within 8 hours of injury, increased recovery of neurological function was seen at 6 weeks and at 6 months and continued to be observed 1 year after injury. For motor function, this difference was statistically significant (p = 0.030), and was found in patients with total sensory and motor loss in the emergency room (p = 0.019) and in those with some preservation of motor and sensory function (p = 0.024). Naloxone-treated patients did not show significantly greater recovery. Patients treated after 8 hours of injury recovered less motor function if receiving methylprednisolone (p = 0.08) or naloxone (p = 0.10) as compared with those given placebo. Complication and mortality rates were similar in either group of treated patients as compared with the placebo group. The authors conclude that treatment with the study dose of methylprednisolone is indicated for acute spinal cord trauma, but only if it can be started within 8 hours of injury.

Acute Disease↗
PubMed1991

Pudendal motor and premotor neurons in the male rat: a WGA transneuronal study.

Anatomical studies using retrograde neuronal tracers were carried out to identify pudendal motoneurons and putative lumbosacral interneurons involved in the generation of penile reflexes in the adult male rat (Sprague-Dawley). In agreement with previous studies, injection of the direct neuronal tracers, horseradish peroxidase or fluoro-gold, into the left M. bulbospongiosus (dorsal division) resulted in direct retrograde labeling of motoneurons only in the ipsilateral dorsomedial (DM) nucleus. In contrast, similar injections of the transneuronal tracer, wheat germ agglutinin (WGA), resulted in direct retrograde labeling of ipsilateral DM motoneurons as well as transneuronal labeling of contralateral DM motoneurons and of bilaterally located putative spinal interneurons. The WGA-labeling was determined to be transneuronal by a series of nerve cut experiments. The direct retrograde WGA-labeling of ipsilateral DM motoneurons and the transneuronal WGA-labeling of contralateral DM motoneurons and bilateral putative spinal interneurons occurred with different time courses. Direct retrograde labeling of ipsilateral DM motoneurons was seen at 20 hours survival and persisted up to 7 days survival. The shortest survival period for detecting transneuronal labeling of contralateral DM motoneurons and putative interneurons was 2 days. Transneuronal WGA-labeling of contralateral DM motoneurons was transient in that the intensity of label increased from 2 to 3 days survival but was markedly reduced at 7 days survival. At the same time, the number of WGA-labeled putative interneurons increased with longer survival times up to 7 days. WGA-labeled putative interneurons were located primarily in regions receiving dendritic projections from WGA-labeled DM motoneurons and, in particular, 1) the ventral gray matter between the DM and dorsolateral nuclei and 2) near the central canal and extending dorsally to the dorsal gray commissure. The rapid and extensive transneuronal transport between DM nuclei suggests that direct synaptic coupling may mediate coordinated, bilateral activation of DM motoneurons.

Animals↗
PubMed1991

Interaction of baseline synaptic noise and Ia EPSPs: evidence for appreciable negative correlation under physiological conditions.

1. In the anesthetized cat, simultaneous intracellular recordings from pairs of spinal motoneurons were undertaken to see whether the amplitude of single-fiber excitatory postsynaptic potentials (EPSPs) in both cells fluctuated in a coordinated manner that would indicate correlative mechanisms at either pre- or post-synaptic level. Although these recordings revealed correlated fluctuations in the baseline, the single-fiber Ia/EPSPs recorded with the spike-triggered averaging technique exhibited no correlated fluctuations and, unexpectedly, virtually no increase in baseline variance associated with the EPSP. However, the fact that these experiments were carried out under conditions of high baseline synaptic noise (i.e., with muscle stretch) may have influenced the outcome because of interaction between EPSP and synaptic noise, and this possibility was evaluated explicitly. 2. A given connection was studied under low noise by electrically stimulating a single Ia fiber in the absence of muscle stretch. The same connection was analyzed under conditions of high noise by activating the fiber and all other stretch receptor afferents with muscle stretch and by using spike-triggered averaging to extract the EPSP. The differences in mean EPSP amplitude at a given connection under conditions of low noise and high noise were minimal. 3. Fluctuations in EPSP amplitude were then determined to see whether these were influenced by presence of baseline synaptic noise and whether the interaction was nonlinear. Two methods were used to measure EPSP fluctuations: measurement of the variance associated with the EPSP, and determination by the use of deconvolution methods of the discrete amplitude components associated with the EPSP. 4. An increase in baseline variance was observed during the EPSP evoked under low noise conditions at all six connections studied in this way. This increase disappeared at two of these connections when examined under high noise. This may help to explain the results obtained in pairs of motoneurons. 5. The deconvolution results were used to calculate the variance of the noise-free EPSP. This was found to differ from the variance of the EPSP amplitude distribution measured directly from the change in baseline variance associated with the EPSP. Analytic techniques suggested that this difference could be explained in most cases by negative correlation between the EPSP and baseline synaptic noise. These considerations led to an analytic method to assess the reliability of the deconvolution result. 6. Simulation studies revealed that the baseline variance increase associated with the EPSP is also highly dependent on the correlation between signal and noise.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1991

The Sterling Hall of Medicine, Yale University School of Medicine.

A brief history of the Sterling Hall of Medicine at Yale University is presented; this building was erected and dedicated in 1925. This event signified the beginning of a new era for the Yale University School of Medicine, making it possible to attract a caliber of faculty that has enabled the School to attain its present place in medical education.

Connecticut↗
PubMed1990

A randomized, controlled trial of methylprednisolone or naloxone in the treatment of acute spinal-cord injury. Results of the Second National Acute Spinal Cord Injury Study.

Studies in animals indicate that methylprednisolone and naloxone are both potentially beneficial in acute spinal-cord injury, but whether any treatment is clinically effective remains uncertain. We evaluated the efficacy and safety of methylprednisolone and naloxone in a multicenter randomized, double-blind, placebo-controlled trial in patients with acute spinal-cord injury, 95 percent of whom were treated within 14 hours of injury. Methylprednisolone was given to 162 patients as a bolus of 30 mg per kilogram of body weight, followed by infusion at 5.4 mg per kilogram per hour for 23 hours. Naloxone was given to 154 patients as a bolus of 5.4 mg per kilogram, followed by infusion at 4.0 mg per kilogram per hour for 23 hours. Placebos were given to 171 patients by bolus and infusion. Motor and sensory functions were assessed by systematic neurological examination on admission and six weeks and six months after injury. After six months the patients who were treated with methylprednisolone within eight hours of their injury had significant improvement as compared with those given placebo in motor function (neurologic change scores of 16.0 and 11.2, respectively; P = 0.03) and sensation to pinprick (change scores of 11.4 and 6.6; P = 0.02) and touch (change scores, 8.9 and 4.3; P = 0.03). Benefit from methylprednisolone was seen in patients whose injuries were initially evaluated as neurologically complete, as well as in those believed to have incomplete lesions. The patients treated with naloxone, or with methylprednisolone more than eight hours after their injury, did not differ in their neurologic outcomes from those given placebo. Mortality and major morbidity were similar in all three groups. We conclude that in patients with acute spinal-cord injury, treatment with methylprednisolone in the dose used in this study improves neurologic recovery when the medication is given in the first eight hours. We also conclude that treatment with naloxone in the dose used in this study does not improve neurologic recovery after acute spinal-cord injury.

Acute Disease↗
PubMed1988

Modulation of EPSP amplitude during high frequency stimulation depends on the correlation between potentiation, depression and facilitation.

High frequency bursts were delivered every 2 s to single group Ia fibers in anesthetized cats. The modulation of EPSP amplitude in target motoneurons was determined. Changes in EPSP amplitude during the high frequency stimulation (facilitation or depression) were correlated with those occurring 2 s after the burst (potentiation). Connections displaying high levels of potentiation exhibited more depression resulting in a net negative modulation. Negative amplitude modulation was greatest at connections on low rheobase ('small') motoneurons that develop large EPSPs. Positive modulation occurred at a subset of connections on high rheobase ('large') motoneurons that exhibit small EPSPs. We suggest that these synaptic properties permit the appropriate amount of depolarization to be delivered to the heterogeneous elements of the motoneuron pool during high frequency Ia fiber activity characteristic of the step cycle.

Action Potentials↗