Faculty Bibliography

The mean value of serum dopamine-beta-hydroxylase (D beta H) in patients with familial dysautonomia, 1 to 5 years of age, does not differ significantly from control children of the same age (24.0 plus or minus 21.06 S.D. as compared to 34.0 plus or minus 33.12). Among patients 6 years of age and over, the mean value was slightly but significantly lower than in control subjects (62.7 plus or minus 49.61, as compared to control values of 86.1 plus or minus 54.31 p less than 0.025). However, the determination of serum D beta H does not contribute to the diagnosis of familial dysautonomia because well over half the children have levels within 1 S.D. of the mean levels of the control subjects. There is no correlation with clinical symptomatology. The disease process may tend to depress the level of serum D beta H but the effect is neither consistent nor decisive

Ascorbic acid stimulates active transport of Cl-minus by the isolated intact cornea. The effect is not present in corneas previously stimulated by the theophylline, an inhibitor of 3':5'-cyclic-AMP phosphodiesterase (EC 3.1.4.17), and vice versa, theophylline has no action after stimulation with ascorbic acid. This indicated inhibition of 3':5'-cyclic-AMP phosphodiesterase by ascorbic acid. Assay of phosphodiesterase using 3-H-labeled cyclid AMP of frog and rabbit corneal epithelial homogenates showed an inhibitory effect of ascorbic acid. Concentration of 5 mM produced 16% inhibition with 20 mM producing 46%. This compares with 58% inhibition by theophylline at 5 mM. Phosphodiesterase activity is mostly soluble in frog corneal epithelium but in rabbit 45% is particulate. Soluble and particulate fractions are inhibited by ascorbate, but in rabbits greater inhibition (50%) was observed in the particulate fraction than in the soluble fraction. Other tissues showed inhibition also: frog retina 12%, rat brain (caudate nucleus) 48%, rabbit brain 14%, rabbit liver 16%. It is concluded that ascorbate produces an increase in cyclic AMP content of corneal epithelium and other tissues by inhibition of 3':5'-cyclic-AMP phosphodiesterase. This action may be one of the main functions of the high ascorbic acid content of ocular tissues and explain some of the effects of high dosis of ascorbate in other systems

To study the possible role of the cerebellum in the vestibular-ocular reflex, extracellular responses of cerebellar nuclear neurons were recorded in awake monkeys during natural vestibular stimulation; 115 neurons in the fastigial nucleus responded to horizontal sinusoidal accelerations applied to the head by means of whole-body rotation. More than 75% of these cells were located in a distinct layer, 500 mum thick, in the rostral part of the fastigial nucleus; they were excited by contralateral horizontal angular acceleration and inhibited by ipsilateral rotation (type IIf neurons). The remaining 25% of the population were scattered more caudally in the nucleus, and were excited by ipsilateral rotation and inhibited by contralateral rotation (type If). All showed fairly high resting discharges, averaging 50 spikes/s. Sinusoidal horizontal rotation (0.2--4.8 HZ) produced clear periodic modulation of the firing rate of fastigial neurons, which was approximately sinusoidal about the resting rate at low frequencies. As the frequency of oscillation (and the applied acceleration) increased, the sinusoidal modulation of unit firing increased in amplitude; at high stimulus frequencies the firing rate was usually driven to zero during the inhibitory part of stimulus cycle, but did not saturate in the excitatory half leading to an increase in the mean firing rate. The maximum firing rates of fastigial neurons were related to the peak acceleration by a power function. At all stimulus frequencies, the peak firing frequency of fastigial neurons lagged the input angular acceleration. Maximum firing of most units occurred just prior to the maximum velocity of the head. The gain and phase lag of the averaged unit discharge relative to head acceleration were calculated by Fourier analysis, using the fundamental as a first approximation of the response. Over a 20-fold stimulus range (0.2--4.0 HZ), mean phage lags of type IIf unit responses with respect to the applied acceleration remained relatively constant; the phase lag at 0.9 HZ measured 62 plus or minus 13 degrees. This phase lag is very similar to that recorded from vestibular nerve fibers (15), suggesting that type IIf fastigial neurons provide an excitatory signal to the ipsilateral vestibular nuclei which is in phase with direct vestibular afferent input, although functionally opposite in sign. Over the same frequency range, the gain decreased at minus- 18 dB/decade. Our data suggests that the majority of fastigial neurons work in parallel with flocculus Purkinje cells to functionally inhibit type Iv neurons in the ipsilateral vestibular nuclei

The antiparkinsonian activity of lergotrile mesylate, a presumed dopaminergic receptor stimulating agent, was investigating in monkeys with surgically induced tremor and in parkinsonian patients. The administration of lergotrile resulted in a dose-dependent reduction in the intensity of tremor in the monkeys. In 13 patients with Parkinson's disease treated with lergotrile (up to 12 mg a day), overall improvement was observed in five. Tremor was the main clinical feature to benefit, and the improvement reached statistical significance. In a subgroup of four patients treated with a higher dose of lergotrile (up to 20 mg a day), further improvement in rigidity and bradykinesia was noted, but again, only improvement in tremor was statistically significant. Adverse effects included orthostatic hypotension, behavioral alterations, and nausea and vomiting. These were severe enough to result in drug withdrawal in three patients

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

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