Faculty Bibliography

The mesencephalic nucleus of the trigeminal nerve (mes V) in the brain of the skate (Raja oscellata) was studied by electron microscopy. Mes V neurons are large (40-80 mum diameter) and are located in the periventricular grey matter. Their perikaryal cytoplasm is rich in Golgi apparatus, small mitochondria, rough endoplasmic reticulum, polysomes and bundles of neurofilaments. A striking feature is the presence of masses of glycogen granules, at times surrounded by membrane wrappings and lysosomal bodies. Two types of conventional synaptic contacts were made onto mes V perikarya and dendrites. One had round, agranular vesicles and usually also contained dense-cored vesicles, the other had flattened, pleomorphic, agranular vesicles and usually lacked dense-cored vesicles. Additional membrane complexes consisting of a region of gap junction flanked by sites of desmosomal attachment were observed to link neighbouring mes V neurons. Somato-somatic, dendro-somatic, axo-somatic, and dendro-dendritic junctions were noted. Except for the somato-somatic union, one or more chemical synapses were located close to the sites of gap junctions.

1. Voltage-clamp experiments were carried out in calf Purkinje fibres to determine the basis of transient depolarizations (TDs) associated with digitalis-induced arrhythmias. 2. Under the influence of strophanthidin, depolarizing clamp pulses were followed by a transient inward current (TI) which was small or absent in untreated preparations. The TI also appeared in the wake of a train of action potentials. 8. The TI can help generate spontaneous depolarizations in preparations showing the low voltage oscillations which often occur with advanced digitalis toxicity. 8. The TI can help generate spontaneous depolarizations in preparations showing the 'low voltage oscillation' which often occur with advanced digitais toxicity. It was designated TI because its magnitude and timing were appropriate to account for the TD. 3. Longitudinal voltage non-uniformity during the TI was determined with two voltage-recording micro-electrodes. Although the non-uniformity was not severe, the TI wave form was observed when the voltage difference signal was used to measure membrane current density. 4. Over the diastolic range of potential, the strophanthidin-induced TI appeared superimposed upon the normal pace-maker mechanism, the decay of a potassium current, iK2. The TI could be dissociated from iK2, however, by means of its unusual kinetic properties. 5. TIs could also be recorded at holding potentials positive to -55 mV, i.e. outside the range where iK2 deactivation occurs. 6. The TI amplitude showed a slow and strongly sigmoid dependence on the duration of the preceding depolarizing pulse. Stronger depolarizing reduced the TI amplitude, while slowing and exaggerating the sigmoid time-dependence. 7. Two clamp pulses in close succession gave additive effects in evoking a subsequent TI. This finding and the sigmoid time-dependence fit with previous observations that TDs are most prominent following a series of closely spaced action potentials

The plasma membrane of myelinated axons in the frog brain has been examined by the freeze-fracture technique. The cytoplasmic leaflet of the axolemma contains numerous randomly distributed particles in nodal and internodal regions but relatively fewer particles in the axoglial junctional portion of the paranodal region. Particle distribution is even less uniform in the outer leaflet of the axolemma, which contains a low concentration of particles in the internodal region and a relatively high concentration at the node of Ranvier (approximately 1200 particles mum-2). The nodal particles tend to be larger than most intramembranous particles, approaching 200 A diameter. The paranodal region of the leaflet is virtually devoid of such particles except in the narrow helical 'groove' which faces extracellular clefts between terminating glial processes. In places this pathway widens to form 'lakes' up to approximately 0.3 mum2 area which contain large numbers of large particles resembling those at the node. The concentration of particles at the node is in the same range as the concentration of sodium channels estimated to be in this region and it is suggested on the basis of their location and concentration that these particles represent ionophores. The distribution of particles in the paranodal region suggests that the large intramembranous particles do not have free access to the axoglial junctional portion of the membrane and therefore the movement of such particles along the paranodal region of the membrane may occur primarily in the membrane of the 'groove' spiraling through this portion of the axolemma. Such a restriction in surface area for particle movements on either side of the node of Ranvier could result in trapping of particles at the node and thus contribute to their concentration in the nodal axolemma.

1. The responses of neuronal elements in the flocculus of the awake, restrained rabbit were recorded during horizontal vestibular nystagmus in the dark. 2. Purkinje cells showed both vestibular (Types I and II) and eye movement modulation of simple spike activity. Type I Purkinje cells most commonly were inhibited in association with the ipsilaterally directed fast phase of nystagmus and excited during contralaterally directed fast phases. Type II Purkinje cells had a similar modulation but in the opposite direction. Variations on this pattern included an increase in firing during fast phases in both directions. 3. Presumed mossy fibers and granule cells also exhibited both vestibular and nystagmic modulation in various combinations. The nystagmic modulation often began during the fast phase and continued into the early part of the slow phase. Mossy fibers showing both vestibular and nystagmic modulation probably arise from the vestibular nuclei and/or the perihypoglossal nuclei. 4. Floccular control of brain stem nuclei utilizes not only vestibular but also eye movement signals and probably all sensory and internal signals involved in the regulation of gaze.

1. The responses of Purkinje cells and presumed mossy fibers to natural stimulation of the horizontal semicircular canals were recorded in the nodulus and uvula of rabbit vestibulocerebellum. Units responding to vestibular stimulation were also studied with visual stimulation. 2. The responses of presumed mossy fibers were of the Type I and Type II varieties and were characterized by a low threshold for angular acceleration and high sensitivity. 3. Purkinje cell responses were divided into two groups: The first group showed only modulation of simple spike activity during rotation. According to the directionality of their responses to rotation, Purkinje cells of the first group could be further subdivided into Types I, II or III; Type II was the most frequently encountered. The second group showed modulation of both simple spike and climbing fiber activity. The simple spike response most frequently encountered was of Type II while the climbing fiber activity in the same Purkinje cells responded in the Type I mode. In another population of Purkinje cells of this group, simple spike activity was modulated by rotation in one direction only. All Purkinje cell responses had relatively high thresholds and low sensitivities. 4. Some Purkinje cells responding to rotation showed direction-selective modulation of climbing fiber discharge in response to slowly moving visual patterns.

Cerebrospinal fluid pathways were studied in both normal and experimental obstructed hydrocephalic cats by positive contrast ventriculography. Either water soluble or insoluble contrast material was injected into the lateral cerebral ventricles, and radiographs were taken of the head and spinal cord. In the normal cat, the contrast material freely flowed throughout the spinal fluid spaces. The contrast material accumulated in the cisterna magna, and from there extended into the cranial and spinal subarachnoid spaces. In the kaolin-induced hydrocephalic cat, the outlets from the fourth ventricle were obstructed, and direct communication between the ventricular system and the subarachnoid spaces no longer existed. In these cats, the contrast material passed directly down the central canal of spinal cord and its movement was followed throughout the entire length of the canal. At the lower lumbar-sacral regions, the material perforated the cord and flowed into the subarachnoid space. At all levels, the central canal was enlarged and local dilatations were seen extending dorsally

1. Measurements of the aspartate-isolated PIII component of the electroretinogram (ERG) were used to estimate photoreceptor threshold in dark-adapted tadpoles of the clawed toad, Xenopus laevis raised on a normal diet. Spectral sensitivity functions established that the rod mechanism governed absolute dark thresholds from stage 40 to the end of premetamorphic development. 2. Parallel measures of rod outer-segment dimensions and visual pigment levels demonstrated a) that visual pigment concentration remained constant at all tadpole stages, and b) that the fall in threshold over the course of premetamorphic development depended exclusively on the increased probability of quantal absorption that accompanied the growth of the rod outer segments. 3. When tadpoles were obtained from vitamin A-deficient females and raised subsequently on a vitamin A-free diet, the first appearance of the ERG was delayed and its absolute threshold raised, with respect to controls. 4. Histological examination of vitamin A-deprived retinas indicated that rod outer segments retained their structural integrity in spite of up to a 75% loss of visual pigment. 5. The threshold rise which accompanied a fall in visual pigment levels, whether effected by dietary deficiency or by bleaching, was greater than could be attributed solely to a reduction in the probability of quantal absorption

Intracellular perfusion of giant axons from Loligo forbesi with a crude protein extract of Pronase dissolved in a KF solution suppresses the process of fast inactivation of the Na conductance (the h-process in the Hodgkin-Huxley terminology). 2. The results with protease inhibitors indicate that the most substrate specific endopeptidase present in pronase, alkaline proteinase b, destroys the h-process. 3. After destruction of the inactivation the conductance rise upon depolarization followed cube law kinetics. Values of the time constant taum before and after destruction of the h-process were very similar. 4. After destruction of the inactivation process the following properties were tested: cation selectivity, instantaneous conductance and internal receptor sites for tetrodotoxin (TTX) and tetraethylammonium (TEA). No detectable changes in selectivity or instantaneous conductance were observed. No internal receptors for TTX affecting the Na conductance were found but a TEA receptor is exposed by the protein hydrolysis. 5. TEA derivatives (triethylammonium, TEA-, with an aliphatic chain, Cn) induce a partial block of the steady-state sodium current and induce a time-dependent blockage of the conductance. 6. The first effect of TEA-Cn could be described in terms of a unimolecular reaction with the following equilibrium constants: 50, 2-5, 1-0, 0-4 and 0-025 mM for TEA-C2, TEA-C4, TEA-C5, TEA-C7 and TEA-C9 respectively. 7. From the dependence of the equilibrium dissociation constant on the length of the alkyl chain we estimated the free-energy change in 560 cal/mole of CH2. The gain in free energy per CH2 group transferred from aqueous medium to the interior of a non-polar medium is 1000 cal. 8. Although with the data at hand it is impossible to propose the amino-acid sequence of the site cleaved by alkaline proteinase b, we propose that an important functional component is arginine (or lysine)