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C J Frederickson

Publications and source records attributed to C J Frederickson.

At least 55 records · Page 3Linked to original sources

Cytoarchitecture and saccular innervation of nucleus y in the mouse.

The cytoarchitecture and saccular innervation of the mouse nucleus y were investigated by using Golgi, Nissl, and myelin stains and anterograde axonal transport of horseradish peroxidase. Nucleus y was found to be a compact group of cells in a small fiber-free region dorsal to the restiform body. Qualitative and morphometric analyses showed that most (75%) of the nucleus y neurons could not be reliably subdivided into morphologic subgroups, but varied continuously in soma size (15-25 microns), shape (fusiform to stellate), and number of dendrites (two to four), and had sparsely branched dendrites with an average of 3 to 4 spines per 10 microns of length. Three groups of cells that were identified morphometrically accounted for 10% (type I: large stellate cells), 9% (type II: long-dendrite cells), and 6% (type III: elongated soma cells) of the y neurons. Vestibular nerve axons transporting horseradish peroxidase after injury at their origin in the saccular neuroepithelium were found to form a dense terminal meshwork that was virtually co-extensive with the cytoarchitectonic boundaries of nucleus y. Nucleus y was distinguished from the overlying infracerebellar nucleus on the basis of anatomical, cytoarchitectural, and hodological features.

Animals↗

Effects of alcohol ingestion on zinc content of human and rat central nervous systems.

The abundance of zinc in hippocampal mossy fibers has stimulated investigation of zinc status in various pathologic states in which behavioral or anatomic deficits involving the hippocampus are known to occur. Limited autopsy studies of chronic alcoholic humans have suggested that the content of zinc might be reduced in several brain regions whereas reported attempts to replicate these findings in ethanol-exposed experimental animals have produced inconsistent results. In this comparative study, the zinc concentration in 10 brain regions, all spinal cord segments, and microdissected hippocampal subfields was measured by isotope ratio mass spectrometry. A widespread 15 to 20% reduction in zinc content was observed in all regions of chronic alcoholics compared with controls but a selective involvement of hippocampus was not detected. In the experimental studies, groups of rats were exposed to ethanol by one of three routes: inhalation for 2 weeks, as an ethanol/liquid diet for 3 months, or a single intoxicating i.p. dose. Determinations of tissue uptake of radiozinc and of total zinc content were made. In contrast to human pathologic material, zinc pool size and tissue uptakes were not affected by experimental ethanol administration by any route. This study confirmed that a reduction in zinc concentration occurs in the central nervous system of chronic alcoholics. The animal studies indicated, however, that simple ethanol exposure, even for prolonged periods, does not perturb zinc metabolism in brain. Together, these observations argue that the abnormalities of zinc metabolism in chronic alcoholics are possibly secondary to homeostatic alterations associated with hepatic failure.

Adult↗

Cholinergic denervation-induced increase of chelatable zinc in mossy-fiber region of the hippocampal formation.

Chelatable zinc has repeatedly been associated with hippocampal mossy fibers, but the neurobiological functions of the zinc have remained unclear. Zinc is a constituent of the 7S Nerve Growth Factor (NGF) molecule. The hippocampal area is rich in neurotrophic factors and cholinergic deafferentation of the hippocampus appears to activate these neurotrophic factors. In this paper we report that cholinergic deafferentation of the hippocampus causes a transient rise in mossy-fiber zinc, as measured by zinc-dithizonate histochemistry. The changes are not significant until 10 days after the septal lesion, and the zinc returns to control levels by 21-28 days. Dithizonate has an association constant of 10(-15) with zinc, while NGF has an association constant of 10(-11). Thus densitometric measurement of zinc dithizone within the hippocampus may be a quantitative histochemical marker of a zinc-associated nerve growth-like substance. The data support recent findings that nerve growth-like factors increase in the hippocampal area following deafferentation, and in addition suggest that zinc is a critical factor in the regulation of trophic phenomena in the hippocampal formation.

Animals↗

Cytoarchitectonic distribution of zinc in the hippocampus of man and the rat.

Zinc was measured in whole hippocampus and in hippocampal sub-regions by stable-isotope dilution mass spectrometry. In both man and the rat, the most zinc (102-145 ppm, dry weight) was found in the hilar region, the least (27-35) in the fimbria. The amount of zinc directly associated with mossy-fiber axons was estimated to be approximately 8% of the total zinc in the hippocampus, and the concentration of mossy-fiber zinc was estimated at 220-300 microM. Methodological and theoretical implications of the quantitative findings were discussed.

Aged↗

In vitro recording of raphe unit activity: evidence for endogenous rhythms in presumed serotonergic neurons.

The spontaneous activity of single neurons in the nucleus raphe dorsalis was recorded in vitro in mouse brain slices. The neurons displayed the slow and regular discharge pattern characteristic of raphe neurons recorded in vivo. When magnesium ion was added to increase the medium concentration to 20-30 mM for the purpose of inhibiting all synaptic transmission, raphe neurons continued to display the same discharge pattern and rate. The data suggest that the steady rhythmic firing of nucleus raphe dorsalis neurons is generated by an intracellular pacemaker mechanism.

Animals↗

Raphe unit activity in freely moving cats: effects of benzodiazepines.

Benzodiazepines (chlordiazepoxide and diazepam) produced a dose-dependent decrease in the discharge rate of serotonin-containing neurons in the dorsal raphe nucleus of freely moving cats. This ranged from no significant change at doses of 0.5 and 1.0 mg/kg (i.p.), to greater than 90% reductions in unit activity at 10 mg/kg. The effects of benzodiazepines on raphe units occurred within 15-30 min of injection and the duration of action was dose-dependent and lasted from 1 to more than 6 hr. Doses of benzodiazepines that significantly decreased raphe unit activity (i.e. 2.5-10 mg/kg) also produced ataxia and decreased EMG activity. These data suggest that benzodiazepine-induced suppression of raphe unit activity is closely related to general motor behavior. Raphe unit activity remained suppressed during phasic increases in EMG activity during eating, grooming, or predatory behavior, suggesting that benzodiazepines also have a direct inhibitory action on raphe cells. The present results are discussed in the context of the serotonergic hypothesis of anxiety.

Animals↗

Emergence of spontaneous alternation in the kitten.

Two studies are reported that describe the development of spontaneous alternation in the kitten. The first indicates that 3- and 4-week-old kittens do not alternate whereas animals 5 weeks and older do alternate. The second suggests that inability to discriminate maze arms is an unlikely explanation for the lack of alternation among the youngest animals. The approximate simultaneity between the onset of alternation (described here) and the maturation of the kitten hippocampus (described by others) is taken as support for the notion that hippocampal maturation may be related to the development of spontaneous alternation.

Aging↗

Developmental changes in open-field behavior in the kitten.

Seventy-eight kittens from 3 to 7 weeks of age were studied in an open-field arena. Three major age-dependent changes were noted: (1) the number of floor squares entered was markedly higher for 5- and 6-week-olds than for younger animals, and slightly lower for 7-week-olds than for 5- and 6-week-olds; (2) the tendency to backtrack from 1 square to a just-vacated square decreased with age, the largest change occurring between 4 and 5 weeks of age; (3) the within-session decrement in locomotion was largest for 3-week-old kittens but was smallest for 4-week-olds and increased monotonically with age thereafter. The results suggest a possible role of hippocampal maturation.

Aging↗

Functional characteristics of cochlear nucleus in behaving cat examined by acoustic masking of electrical stimuli.

1. Cats were trained, using an operant procedure, to detect and respond to electrical stimulation delivered in the vicinity of the cochlear nucleus. The electrical stimuli were presented both in silence and in synchrony with repeated noise bursts to determine whether detection thresholds for the electrical stimuli were elevated by the acoustic masking noise. 2. For stimulation sites centered within auditory structures (cochlear nucleus or acoustic nerve root), the acoustic maskers caused a consistent elevation of the electrical detection thresholds. For stimulation sites that were in or bordered on nonacoustic neural structures (e.g., vestibular), the acoustic maskers caused little or no elevation of electrical detection thresholds. 3. The magnitude of the acoustic masking effect was monotonically related to the intensity of the acoustic masker across the range of intensities tested. 4. The magnitude of the masking effect was strongly dependent on the relative timing of the stimulus pulse and the masker noise burst. Maximum masking occurred when the pulse just followed the onset of the neural activity in cochlear nucleus evoked by the masker burst. Less masking occurred when the electrical pulse occurred at the middle or end of the masker burst, and still less when the pulse occurred just prior to the onset (backward masking) or just after the offset (forward masking) of the masker burst. 5. The magnitude of the masking effect also depended on the frequency of the acoustic masker. For tone bursts, masking was maximal for each electrode at a particular frequency and declined monotonically for masker frequencies above or below the optimal frequency. 6. It is concluded that the masking of an electrical stimulus by an acoustic stimulus depends on a direct interaction between the neural responses evoked by the two stimuli, and that similar central, neural interactions may contribute to acoustic masking of acoustic stimuli. It is also concluded that the technique of masking an electrical stimulus by an acoustical stimulus is a precise and useful tool for the study of sensory-neural organization in intact behaving animals.

Animals↗

Effects of sleep deprivation on awakening thresholds and sensory evoked potentials in the rat.

The EEG desynchronization response to stimuli presented during slow-wave sleep was studied in 25 chronically implanted rats after 12 hr of sleep deprivation and during control periods of normal sleep. Compared to normal sleep, sleep after deprivation was accompanied by a significant decrease in the number of EEG desynchronization responses to auditory stimuli and by an additional disproportionate decrease in the number of sustained desynchronization responses. Thalamic auditory evoked potentials were not reduced in amplitude during postdeprivation sleep, thus the decrease in number of EEG desynchronization responses to the auditory stimuli was apparently not mediated by decreased responsiveness in the peripheral auditory system. On the other hand, postdeprivation sleep was not accompanied by any significant change in total number of EEG desynchronization responses to direct trigeminal nerve stimulation nor by any change in the duration of responses to trigeminal stimulation. The results suggest that recovery from sleep loss in accompanied not by a nonspecific increase in the threshold for arousal per se but instead by a selective increase in the threshold for arousal to certain classes of peripheral stimuli.

Acoustic Stimulation↗

Masking of electrical by acoustic stimuli: behavioral evidence for tonotopic organization.

When pure-tone acoustic masking stimuli of various frequencies were presented simultaneously with electrical stimuli applied to cochlear nucleus, only those maskers within a limited frequency range interfered with the detection of the electrical stimuli. The form of the masking functions obtained suggest that the electrical stimulus directly activated only a small population of neurons which were functioning in a tonotopic fashion.

Acoustic Stimulation↗