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P Pasik

Publications and source records attributed to P Pasik.

At least 19 recordsLinked to original sources
PubMed1992

Amino acids and N-acetyl-aspartyl-glutamate as neurotransmitter candidates in the monkey retinogeniculate pathways.

The identity of the neurotransmitter(s) in the mammalian retinogeniculate pathway is unclear. To investigate the possibility that some amino acids and certain dipeptides, such as N-acetyl-aspartyl-glutamate (NAAG), fulfill this function, changes in their concentration were measured in the optic tract, and the parvocellular and magnocellular segments of the LGNd of six monkeys (Macaca fascicularis), seven days after right optic tractotomy. The LGNd was studied also in two additional macaques, three months after occipital lobectomy. Tissue was frozen within five minutes of death, regions were dissected with the micropunch technique, and substances were analyzed by HPLC. Optic tractotomy induced significant, large reductions in NAAG, glutamate and aspartate in the optic tract distal to the lesion. Significant decreases in NAAG were also measured in the LGNd, and these changes were apparent in both the parvocellular and magnocellular segments. A small reduction in glutamate reached significance in the parvocellular laminae, and that of aspartate only approached significance in the magnocellular division. Occipital lobectomy produced large declines in aspartate and glutamate in the LGNd. The results of optic tractotomy support the role of NAAG as a neurotransmitter candidate in the monkey retinogeniculate pathways; its significant decrease in both geniculate segments suggests that both P- and M- retinal axons utilize this substance. Although at times the reductions in glutamate or aspartate failed to reach significance, their role cannot be excluded. The findings after occipital lobectomy strongly favor these latter substances as corticogeniculate and/or geniculocortical transmitters.

Amino Acids↗
PubMed1992

Monoclonal antibodies for ultrastructural visualization of L-baclofen-sensitive GABAB receptor sites.

Monoclonal antibodies were raised against the L-enantiomer of baclofen conjugated by glutaraldehyde to keyhole limpet hemocyanin. Hybridoma clones were selected for their stability and their production of high titers of antibodies directed against the p-chlorophenyl moiety of the L-baclofen molecule. The chosen antibody showed no cross-reactivity with conjugates of GABA and other neurotransmitters to human or bovine serum albumin. Specificity was further confirmed by the ability of L-baclofen-HCl to inhibit the binding of the antibody to L-baclofen-bovine serum albumin conjugate. Immunocytochemical studies were conducted on brain tissue from rats and monkeys injected with baclofen to localize baclofen-sensitive GABAB receptor sites. In these animals, the molecular layer of cerebellar cortex was clearly immunostained and the granular layer showed only some pale immunoreactivity. Ultrastructural observations were conducted in cerebellar cortex, as well as in the substantia nigra and the vestibular nuclei. Discrete labeling of neuronal profiles was observed in these structures, and both immunoperoxidase and colloidal gold methods were employed successfully. Material from saline-injected control animals showed no immunoreactivity at both light and electron microscopic levels. We conclude that the anti-L-baclofen antibody preferentially recognizes the p-chlorophenyl moiety of the baclofen molecule. Antibodies of such specificity are useful tools for the ultrastructural localization of baclofen-sensitive GABAB receptor sites. In general, antibodies directed against accessible moieties of specific neuroactive substances may serve as valuable markers for their sites of action.

Animals↗
PubMed1992

A membrane model for cytosolic calcium oscillations. A study using Xenopus oocytes.

Cytosolic calcium oscillations occur in a wide variety of cells and are involved in different cellular functions. We describe these calcium oscillations by a mathematical model based on the putative electrophysiological properties of the endoplasmic reticulum (ER) membrane. The salient features of our membrane model are calcium-dependent calcium channels and calcium pumps in the ER membrane, constant entry of calcium into the cytosol, calcium dependent removal from the cytosol, and buffering by cytoplasmic calcium binding proteins. Numerical integration of the model allows us to study the fluctuations in the cytosolic calcium concentration, the ER membrane potential, and the concentration of free calcium binding sites on a calcium binding protein. The model demonstrates the physiological features necessary for calcium oscillations and suggests that the level of calcium flux into the cytosol controls the frequency and amplitude of oscillations. The model also suggests that the level of buffering affects the frequency and amplitude of the oscillations. The model is supported by experiments indirectly measuring cytosolic calcium by calcium-induced chloride currents in Xenopus oocytes as well as cytosolic calcium oscillations observed in other preparations.

Animals↗
PubMed1991

The magnocellular and parvocellular divisions of the monkey subthalamic nucleus as revealed by cluster analysis of neuronal sizes.

Cluster analysis of neuronal somal sizes in the subthalamic nucleus of rhesus monkeys from newborn to adult age allows the segregation of two territories with predominance of small and large cells, respectively. The topographic distribution of the 'parvocellular' and 'magnocellular' segments is similar when samples are obtained from coronal, horizontal and sagittal series of sections. The parvocellular component occupies the rostral pole, the entire rostrocaudal extent of the medial tip and dorsomedial border, and probably also the caudal cap. The magnocellular segment is in the central core extending to the ventrolateral border except for the medial tip. These findings and their correlation with the results of other morphologic and physiologic studies allow the following conclusions. (1) The monkey subthalamic nucleus contains at least two differentially distributed cell subpopulations. (2) The magnocellular division is more related to the pallido-subthalamic-pallidal loop involving the lateral pallidal segment. (3) The parvocellular division appears strategically located to control the pallidal output to diencephalic and mesencephalic targets. (4) Cluster analysis can reveal the existence of more than one neuronal population in a particular brain structure where an overall unimodal distribution of cell sizes may suggest the presence of a single type.

Aging↗
PubMed1991

Acetyl-levo-carnitine protects against MPTP-induced parkinsonism in primates.

Acetyl-levo-carnitine (ALC) protects against 1-methyl, 4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced toxicity in the nonhuman primate. ALC pretreated monkeys do not show signs of parkinsonism or electroretinographic changes typical of dopaminergic deficiency when given MPTP. In addition, pilot neurochemical and morphological data confirm a partial protection effect. While MAO-B inhibitors, like L-Deprenyl, are thought to protect dopaminergic neurons from MPTP-induced cell death by preventing the conversion of MPTP to its toxic metabolite MPP+, ALC is not known to have MAO-B affinity. Converging evidence suggests that ALC may affect directly mitochondrial respiration, which is known to be the target of MPP+ and affected in human neurodegenerative diseases, including Parkinson's disease. The results of this study point to new therapeutic avenues for the treatment of these nosologic entities.

Acetylcarnitine↗
PubMed1991

Different types of synaptic triads in the monkey dorsal lateral geniculate nucleus.

Characteristic synaptic complexes, the triadic synapses, were investigated in long series of sections of parvicellular and magnocellular laminae of the monkey lateral geniculate nucleus. Electron microscopic observations revealed the presence of different triadic types, the intercalated element being in all cases a presynaptic dendrite or soma of an interneuron (I-cell), and the output component being constantly a dendrite or soma of a geniculocortical projection or principal neuron (P-cell). The axonal input to the triads, however, was found to be of three different types: (1) the majority were retinal axon terminals; (2) a smaller fraction were the axonal endings of corticogeniculate fibers, always connected to thin, distal P-cell dendrites; (3) others were terminals with pleomorphic or flattened, small synaptic vesicles, probably belonging to axons of I-cells and/or of thalamic reticular nucleus origin. It was observed also that the retinal terminals established multiple synaptic contacts with both P-cell and I-cell dendrites. Essentially, two types of triadic arrangements with retinal input were recognized: the "simple" unit, frequent in parvicellular laminae, in which the retinal axon was accompanied by only 1-2 presynaptic dendrites; and the "complex" unit, found mostly in the magnocellular laminae, characterized by the presence of up to eight presynaptic dendrites. In the glomerular "complex" units, "closely packed" classical triads, with the three synaptic junctions localized close to each other, coexisted with triads "at a distance" where the synapses were distributed relatively far from each other. The coupling by presynaptic dendrites of "closely-packed" and "at a distance" triads resulted in the formation of multiple triadic arrangements. Since cortical and inhibitory triads were never seen to be involved in multiple triadic complexes, the latter appeared exclusively retinal in nature. The possible functional significance of multiple triads in "ON-gating" operation is briefly discussed.

Animals↗
PubMed1990

On the dynamics of triadic synaptic arrangements: computer experiments with formal neural nets of chaotic units.

Computer simulations were carried out in an attempt to understand the possible operating modes of synaptic triadic arrangements as described in the dorsal lateral geniculate nucleus of the monkey. Small networks of "chaotic" units (piecewise linear internal maps) were used to investigate their performance as ON-gates for the transmission of spikes. "Chaotic" units have advantages over "logic" units because the former are asynchronous, it is possible to simulate temporal summation, and also to adjust subthreshold time-constants. It was demonstrated that ensembles with single delay lines, representing "closely-packed" triads, were hardly capable of realizing reliable and efficient ON-gate operations. Networks with multiple delayed lines, patterned after triads "at a distance" coupled with "closely-packed" triads, were capable of secure ON-gate functions. Such gates were input dependent, becoming reliable only when high frequency bursts were used as the source of activity. Moreover, the ON-gate could be temporarily interrupted by square wave bursts applied to the inhibitory units, a situation resembling electron microscopic observations of interneuron to interneuron synapses in the LGNd.

Computer Simulation↗
PubMed1989

Early postnatal development of the monkey globus pallidus: a Golgi and electron microscopic study.

The globus pallidus of 20 monkeys ranging in age from newborn to 4 months was examined in Golgi-impregnated material and ultrastructurally. There was no discernible difference between the lateral and medial segments of the structure. At the light microscope level, all neuronal types described in the adult are found at birth. The most common, the large fusifom cell, shows initial signs of immaturity such as blunt protrusions and dendritic dilations at bifurcation points, as well as growth cones, filopodia, and filiform processes. These features become more rare with age, and by 4 months, the neurons appear fully mature save for the terminal dendritic arborizations which are still underdeveloped. From the earliest ages examined, the large globular cells and the interneurons are more mature than the previous type. The afferent radial fibers of striatal origin are observed from birth, but they are grouped in bundles only after 8 weeks. The density of their climbing branches increases over time, reaching a mature appearance by 16 weeks. Afferents entering from the ventral surface do not yet show clusters of varicosities at 2 weeks. At the latter age, plexuses of fine beaded fibers are already seen covering large extensions of the nucleus. The fine structure correlates well with the Golgi material. The basic features of the neuropil are present at birth, albeit with immature characteristics such as the incomplete covering of the dendrites with axonal boutons and the low level of myelination of the radial fibers. Growth cones and profiles with signs of degeneration are observed during the first month. In the early ages examined, most dendrites show large varicosities and protrusions, some of which are spinelike and can be postsynaptic to multiple terminals. The other dendritic type, with only an occasional axodendritic synapse, is also seen from birth and increases in size as a function of time. The type I axonal boutons, of probable striatal origin, are quite immature at birth, and their characteristic interdigitations are seen only after the first week. The type II, III, IV, and V boutons appear mature at all ages examined but crest synapses formed by the type III terminals are observed in the later stages of the study. Finally, postsynaptic vesicle-containing profiles are present at 4 weeks, but triadic synaptic arrangements are formed only by 16 weeks.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1988

GABAergic elements in the neuronal circuits of the monkey neostriatum: a light and electron microscopic immunocytochemical study.

An antibody raised in rabbits against a GABA-BSA conjugate was used together with the PAP technique to label elements in the neostriatum of three Old World monkeys. Light microscopy revealed numerous immunoreactive medium-size neurons of various staining intensities, some of which had indented nuclei, as well as an occasional large cell. The neuropil showed a plexus of fine processes with frequent puncta. Ultrastructurally, the medium-size GABA-positive neurons were of two types: one with smooth nuclei and scanty cytoplasm, similar to spiny I cells, the other with invaginated nuclear envelopes and more abundant perikaryon, resembling the aspiny type. Correspondingly, labeled dendrites were either spiny or varicose. Some stained axons were myelinated, and the boutons had either large and ovoid, or small and pleomorphic vesicles. All of these boutons formed symmetric synapses, the former type with GABA-positive dendritic shafts but also with unlabeled dendrites; the latter type usually with GABA-negative elements, either dendrites, dendritic spines, or somata. Synapses were also observed between unreactive boutons and immunostained dendrites. Terminals with densely packed, small round vesicles that established asymmetric synapses with spines were always GABA-negative. Glial elements were consistently unlabeled, save for some astroglial endfeet. These findings provide positive evidence for the existence of two classes of GABAergic striatal neurons corresponding to a long-axoned spiny I type and an aspiny interneuron. Furthermore, the simultaneous labeling of GABA-immunoreactive presynaptic and postsynaptic profiles offers possible morphologic bases for the various kinds of intrastriatal inhibitory processes, including the feedforward, feedback, and "autaptic" types.

Animals↗
PubMed1988

Serotonin-immunoreactivity in the monkey lateral geniculate nucleus.

Serotonin-immunoreactivity in the monkey lateral geniculate nucleus appears as a plexus of fine, beaded fibers decreasing in density from magnocellular to parvocellular laminae. Ultrastructurally, these fibers show strictures and dilations, and are filled with dense round particles as well as granular material attached to outer mitochondrial membranes and microtubules. Most of the profiles followed in serial sections lack morphologically defined synapses. The few synapses observed are asymmetric, some with subjunctional dense bodies. This appearance suggests a possible excitatory effect mainly on interneurons which in turn would inhibit principal cells. Serotonin released non-synaptically may block the delivery of transmitters from retinal terminals and/or the receptors for such transmitters, thereby exerting a modulatory depressing action on principal cells.

Animals↗
PubMed1987

Early postnatal development of monkey subthalamic nucleus: a light and electron microscopic study.

The subthalamic nuclei of 9 rhesus monkeys, ranging in age from newborn to 17 weeks, were examined at the light and/or electron microscopic levels, using computer assisted quantitative methods. The volume of the structure does not change significantly over the period of study. The mean cross-sectional area of neuronal somata, however, decreases by 33%, and most markedly during the first month. This is paralleled by a similar change in the mean area of cell nuclei but the perikaryon/nucleus ratio increases steadily after the first week. There is an overall decline in total cell numbers from newborn to 17 weeks. Ultrastructural features include dendritic growth cones in the neonatal monkey, and signs of axonal degeneration during the entire period. In addition to conventional axosomatic and axodendritic synapses, there are also synaptic junctions between vesicle-containing profiles which are seen only after the first month. The distributions of plaque diameters were reconstructed by the Coupland stereologic method from linear measurements of synaptic profiles and used to calculate synaptic densities and estimate the total number of synapses. This number is stable during the first postnatal month, declines markedly in the second month, and to a lesser degree thereafter, reaching a value of 55% of that at birth by 16 weeks. Findings indicate the occurrence of substantial changes within the subthalamic nucleus during the first 4 postnatal months, the most prominent of which is a marked synapse elimination.

Aging↗
PubMed1986

Synapses between GABA-immunoreactive axonal and dendritic elements in monkey substantia nigra.

gamma-Aminobutyric acid (GABA)-positive elements in the monkey substantia nigra pars reticulata (SNr) were identified using the peroxidase-antiperoxidase immunocytochemical technique with a direct GABA antibody. Light-microscopic examination revealed fine-caliber immunostained fibers piercing the cerebral peduncle and entering the SNr, where they formed a dense plexus. Ultrastructural observations included boutons with densely packed ovoid synaptic vesicles forming synapses with labeled and unlabeled dendritic elements. Most terminals contained small dark mitochondria, although some endings held larger, paler and fewer of these organelles. The synapses observed between GABA-immunoreactive profiles may represent the morphologic basis for disinhibition of pars compacta neurons reported to follow neostriatal or pallidal stimulation.

Aging↗
PubMed1986

A newly recognized element in the monkey dorsal lateral geniculate nucleus exhibiting both presynaptic and postsynaptic sites.

The dorsal lateral geniculate nucleus (LGNd) of four normal monkeys (Macaca mulatta) and of two other such animals with total unilateral ablation of the visual cortices (4-6 days survival) were examined in serial thin sections with the electron microscope. In these materials we have observed a new neuropil component which has the cytologic characteristics of principal cell (P-cell) dendrites, i.e. large and dark mitochondria, smooth endoplasmic cisterns and filamentous, non-synaptic contacts with retinal terminals. In addition, these elements contain large round synaptic vesicles and can be seen forming asymmetric synapses exclusively with presynaptic dendrites belonging to interneurons (I-cells). Occasionally, a reciprocal synapse is formed between the two profiles. The novel elements are postsynaptic to various vesicle-containing profiles, i.e. axonal boutons of presumably retinal and cortical origin, and I-cell presynaptic dendrites. They are found more frequently in the specimens with cortical ablations, although their number is still much lower than that of the other classic components of the neuropil. Measurements made on X 80 000 electron micrographs of spheroid vesicles within presumptive retinal terminals, cortical endings and the new profile described in this report, result in mean diameters of 38.6 nm, 33.3 nm and 44.3 nm, respectively. The differences between the means are statistically significant. Although the profile with large dark mitochondria and large round vesicles may represent a dendrite of a different I-cell type, or a recurrent axon collateral of a P-cell, it appears more probable that it is a presynaptic dendrite of a P-cell. The infrequent but consistent occurrence of these elements suggests that at least some P-cells can develop presynaptic sites on their dendrites, a property which contributes to the synaptic complexity of the LGNd.

Animals↗
PubMed1985

Early postnatal development of the monkey visual system. II. Elimination of retinogeniculate synapses.

Profiles of retinal terminals, and of their synaptic and non-synaptic contacts, were measured in electron micrographs from magnocellular and parvocellular laminae of the dorsal lateral geniculate nucleus (LGNd) in newborn, 1-,4-,8- and 17-week-old rhesus monkeys. Morphologic criteria, i.e., the presence of pale mitochondria and large round vesicles, were used to identify the profile of retinal origin. Size-frequency histograms were stereologically reconstructed and used to calculate the density of retinal boutons and synaptic and non-synaptic plaques. The density values were adjusted for laminar growth to yield estimates of total numbers of these elements. Numerical estimates indicate bouton proliferation during the first week, followed by substantial reductions in bouton number accompanied by profound decreases in synapse number and cumulative synaptic area. In magnocellular layers, the reduction in synapse number is more pronounced after the eighth week, whereas the decrements in both features in the parvocellular laminae occur before this time. This synapse elimination process may be due entirely to retinal bouton retraction in parvocellular layers, but involves additional retinal synapse loss in the magnocellular segment. The parvocellular division shows a further size contraction of the remaining synapses. Immature synapses predominate in the LGNd throughout the 4-month period, and no quantitative evidence for direct transformation of immature to mature contacts is obtained. Non-synaptic junctions are stable in number but of increasing size in magnocellular layers, whereas substantial increases in number and area are found in parvocellular laminae. The preceding modifications in synaptic organization of the monkey LGNd occurring during the initial postnatal period may provide morphologic bases for the physiological and behavioral changes observed in this species during the same interval. Our data underscore the conclusion that synaptic reorganization occurs over a prolonged period, probably extending beyond 4 months, and involving the process of synapse elimination.

Animals↗
PubMed1985

Early postnatal development of the monkey visual system. I. Growth of the lateral geniculate nucleus and striate cortex.

The postnatal growth of the dorsal lateral geniculate nucleus (LGNd) and the striate cortex (SCx) was compared in the same monkeys, by estimating LGNd volume, and the volume, surface area, and thickness of the SCx at birth, 1, 2, 4, 8 and 17 weeks. Shrinkage during histologic manipulations was determined in individual animals, and the above measurements were adjusted accordingly so that final volumes reflected a common, and, therefore, comparable state before processing. The volume of the LGNd increases approximately 17% between 2 and 4 weeks, and this growth primarily reflects that of the parvocellular laminae, the magnocellular components contributing a stable amount in absolute terms. Lamina 1 is larger than lamina 2 at all ages sampled. In contrast, the SCx expands about 75% in volume from birth to the oldest age examined without reaching an asymptote during the period of study. During the first 2 postnatal months, the growth results from increases in the thickness of the SCx whereas in the second 2 months it is caused by expansion in surface area. A comparison of exposed vs buried SCx does not reveal differences in the developmental patterns of regions subserving central vs peripheral visual fields, respectively, the exposed cortex being consistently greater in volume and area but thinner than the buried segment. No significant right/left asymmetries are found across the subjects in either of the structures studied. The findings indicate that the early postnatal development of the monkey visual system proceeds in a sequential fashion with the LGNd preceding that of the SCx.

Animals↗