Faculty Bibliography

Dibutyryl cyclic AMP (dB-cAMP) elicits a concentration-dependent stimulation of tyrosine hydroxylase activity in the striatal and mesolimbic synaptosomes. The per cent of stimulation is significantly higher in the mesolimbic synaptosomes than in the striatal synaptosomes. dB-cAMP and depolarizing agents (ouabain or veratridine) have an additive effect on synaptosomal tyrosine hydroxylase activity, indicating that they stimulate tyrosine hydroxylase activity by different mechanisms. cAMP does not stimulate soluble striatal tyrosine hydroxylase activity unless it is added in combination with ATP and Mg2+, compounds required for the activity of cAMP-dependent protein kinase. The cAMP elicited per cent stimulation of soluble tyrosine hydroxylase activity is dependent upon the concentration of added protein kinase and upon the pH of the reaction. dB-cAMP has the same effect on the kinetic state of tyrosine hydroxylase in synaptosomes as cAMP on the soluble tyrosine hydroxylase. The nucleotide does not alter the apparent Km for tyrosine, reduces the Km for the pteridine cofactor and increases the Ki for dopamine. Thus, cAMP increases the affinity of tyrosine hydroxylase for the pteridine cofactor and concomitantly decreases the affinity for the end-product inhibition.

The effects of ventricular fluid osmolality on the bulk flow of nascent fluid into the cerebral ventricles of anesthetized cats was measured during ventriculocisternal perfusion. This nascent fluid consists of both cerebrospinal fluid (CSF) and fluid which results from an osmotic gradient between ventricular fluid and the blood and/or brain. Perfusions were carried out with both mock CSF and with solutions containing either sucrose, urea, or NaCl. Differences between the normal bulk flow rate of nascent CSF and bulk flow rate measured during perfusion with anisotonic solutions were linearly related to corresponding differences in osmolality of the effluent fluid from the ventricles. The coefficients of somotic flow using sucrose (0.231 mul/min per mOsm) and NaCl (0.224) were similar, and greater than that using urea (0.156). During perfusion with sucrose when effluent osmolality increased by 200 mOsm (63% of normal), bulk flow rate of nascent fluid increased by 50 mul/min (200% of normal). Flow was undetectable when the effluent osmolality was 190 mOsm (decrease of 135 mOsm), although osmotically active particles continued to enter the ventricular system. Intravenous injection of acetazolamide reduced these coefficients to similar values of 0.0963 for NaCl, and 0.0955 for urea. In all experimental conditions no changes were found in cerebral water content. These results suggest that the increased bulk flow which occurs during perfusion with hypertonic solutions originates from the choroid plexus.

The antiparkinsonian activity of bromocriptine, a presumed dopaminergic receptor agonist, was investigated in monkeys with surgically induced tremor and in a group of parkinsonian patients. A single administration of bromocriptine resulted in a dose-dependent relief of tremor in monkeys. Repeated administration enhanced this effect. Only mild abnormal involuntary movements were observed and only after repeated administration. Eleven patients with Parkinson's disease were treated with bromocriptine (mean dose, 26.4 mg a day). Clinically obvious improvement was noted in one or more of the cardinal signs of the disease in six patients (responders). No obvious improvement in any of the cardinal signs was noted in the remaining five patients (nonresponders). Clinically, the responders were older and more severely affected and had been on a higher dose of levodopa. However, they had had the disease for a shorter period. It is suggested that failure to respond to bromocriptine may be related to a decrease in the sensitivity of postsynaptic dopaminergic receptors

Computed tomography (CT) is a safe and reliable technique for the study of children with increased head circumference. Hydrocephalic children requiring drainage of cerebrospinal fluid may be shunted on the basis of the CT scan alone and their postsurgical course followed by serial CT scans thereafter. Any additional pneumographic studies required may be performed via the existing shunt tube, eliminating transcerebral catheterization and its attendant complications

Effects of changes in serum osmolarity on volume flow of fluid into the cerebral ventricles of cats were measured by ventriculocisternal perfusion with mock cerebrospinal fluid (CSF), mock CSF containing acetazolamide, or a 30 mOsm/liter sucrose solution. Serum osmolarity was altered by intravenous infusion of a sucrose solution ranging between 10 and 650 mOsm/liter changing volume flow. For all perfusion fluids, regression lines relating volume flow to infused solution osmolarity were parallel. After infusion of a 10 mOsm/liter solution, brain water content increased. One hour after infusion, volume flow returned to normal, although serum was still hypotonic. Gray matter water content was still elevated; white matter returned to normal. The results suggest that the source of increased volume flow is the brain, and that the CSF acts as a sink, limiting excess water accumulation during water intoxication.

It is well known that cardiac action potentials are shortened by increasing the external calcium concentration (Cao). The shortening is puzzling since Ca ions are thought to carry inward current during the plateau. We therefore studied the effects of Cao on action potentials and membrane currents in short Purkinje fiber preparations. Two factors favor the earlier repolarization. First, calcium-rich solutions generally raise the plateau voltage; in turn, the higher plateau level accelerates time- and voltage-dependent current changes which trigger repolarization. Increases in plateau height imposed by depolarizing current consistently produced shortening of the action potential. The second factor in the action of Ca ions involves iK1, the background K current (inward rectifier). Raising Cao enhances iK1 and thus favors faster repolarization. The Ca-sensitive current change was identified as an increase in iK1 by virtue of its dependence on membrane potential and Ko. A possible third factor was considered and ruled out: unlike epinephrine, calcium-rich solutions do not enhance slow outward plateau current, ikappa. These results are surprising in showing that calcium ions and epinephrine act quite differently on repolarizing currents, even though they share similar effects on the height and duration of the action potential

Standard techniques for performing carotid angiography in dogs and in man were adapted to the cat in order to study the vascularization of both intracranial and extracranial structures. Venous drainage was examined by venography of selected vessels. The carotid-cerebral and the vertebral-basilar arterial systems of the cat were studied, although no attempt was made to define the territory supplied by each system. In serial angiograms, vascularization of the rete mirabile conjugatum was visualized and distinct arterial and venous retia were delineated. Large facial veins were seen approximately one second after the intra-arterial injection of radio-contrast material. The early filling of the large facial veins appeared to be the result of an artery-to-venous shunt. Contrast material flowed posteriorly in these veins and drained into the venous rete. When contrast material was injected either into the sagittal sinus or retrograde in the external jugular vein, the internal jugular vein was visible in four of ten cats. This vessel drained blood directly from intracranial contents before anastomosis with the vertebral and external jugular veins

1. The electrophysiological properties of the EPSP generated in Purkinje cells by the activation of CFs were studies in the cat cerebellar cortex. 2. CF-EPSPs were evoked by electrical stimulation of the cerebellar white matter and recorded intracellularly from the soma of the Purkinje cells. 3. Current was injected into the Purkinje cells via the recording micropipette using a bridge amplifer in order to study the reversal properties of the EPSP. 4. The CF-EPSP reversal was biphasic with the early portion reversing first. 5. The reversed EPSP waveform was not a mirror image of the EPSP, but displayed a briefer time course. 6. A four-compartment computer stimulation showed that the reversal properities of the CF-EPSP were explicable in terms of a distributed synapse on a cable. 7. The biphasic reversal and asymmetry were shown to be due to the spatially nonuniform potential distribution created by the somatic current injection, which predominantly reversed the proximal part of the distributed synapse. Delayed rectification may also have contributed to the reversal asymmetry. 8. The advantages of a distributed synapse over a point synapse are discussed and the reversal properties of the CF-EPSP compared to those of the Ia-evoked EPSP in motoneurons.