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P Pasik

Publications and source records attributed to P Pasik.

17 recordsLinked to original sources

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

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

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

Downward gaze in monkeys: stimulation and lesion studies.

Ten monkeys were stimulated unilaterally and bilaterally through bipolar electrodes placed stereotactically on each side of the midline under light barbiturate anaesthesia. Bilateral simultaneous stimulation elicited straight downward binocular movements from a core of tissue about 40 mm3 on each side which included the fields of Forel, zona incerta, subthalamic nucleus, oral pole of the red nucleus, fasciculus retroflexus and 'area tegmentalis'. Unilateral stimulation of the same points yielded downward eye movements in only 25 per cent of the instances. Upward deviation of the globes could be elicited by bilateral stimulation of tissue located more caudal, ventral and medial than that from which downward movements were obtained. Bilateral electrolytic lesions within the region outlined above caused significant defects in downward gaze both in saccadic and slow pursuit binocular movements. Passive bending of the head backwards, however, resulted in downward deviation of the globes (oculocephalic reflex). Optokinetic nystagmus and after-nystagmus downward were abolished. Oblique (45 degrees) optokinetic stimulation elicited a perverted response in the horizontal plane. Vestibulo-ocular reflexes elicited by bilateral warm irrigation of both ear canals with the monkey in the erect position, or by turning the animal while lying on one side, caused a strong tonic deviation upward with absence of nystagmus downward. Some of these monkeys showed additional alterations in upward gaze but they were less severe in intensity and duration than those of downward gaze. All eye deviations in the horizontal plane were consistently normal. Recovery occurred in all types of vertical binocular movements except in the rapid motions (saccades and quick phases of nystagmus) below the horizontal meridian. A unilateral lesion had no effect. The minimal damage producing downward gaze defects was about 1.7 mm in diameter, cetred in the prerubral fields, rostral and medial to the red nuclei with minimal involvement of the oral pole of these structures. The nuclei of Cajal, Darkschewitsch and interstitialis of the posterior commissure, as well as the fasciculus retroflexus and the posterior commissure, were spared by this lesion. The so-called rostral interstitial nucleus of the medial longitudinal fasciculus and the nucleus campi Foreli appear to be destroyed. These structures are known to receive an input from the paramedian pontine reticular formation and project on to the oculomotor nerve nucleus. These results demonstrate that the prerubral fields contain structures which are critical for rapid eye movements downward, and therefore an isolated downward gaze palsy is a strong indicator of a bilateral lesion of this zone. The findings in the few reported cases with this sign and available pathological analysis suggest that our conclusions from the experimental monkey apply to man as well. The concept of bilateral innervation for vertical eye movements is amply confirmed for the downward vectors...

Animals

A Golgi study of neuronal types in the neostriatum of monkeys.

Examination of the nestriatum of monkeys prepared by the Golgi-Kopsch perfusion method revealed the presence of at least 6 neuronal types. The spiny type I is medium size with a high density of dendritic spines. The axon extends well beyond the dendritic field and gives off many collaterals. The spiny type II is either medium or large size, has long thick dendrites with a relatively low density of spines, and an axon similar to that of the previous type but with fever collaterals. The aspiny type I is medium size with varicose dendrites and a thin axon arborizing in the immediate vicinity of the soma. The aspiny type II is large, with many thick and thin varicose dendrites. The aspiny type III is medium size with smooth dendrites and an axon ramifying profusely within the dendritic field. The neurogliform cell is small with many branching processes. Findings indicate that the neostriatum has 2 distinct types of spiny neurons with long axons (spiny I and II), some of which may contribute to the efferent system. There are also 2 (aspiny I and III) or perhaps as many as 4 categories (aspiny I, II, III and neurogliform) of typical Golgi type II cells. Large neurons belong to 2 separate populations, one with dendritic spines and a long axon (large version of spiny II), and one with varicosities and presumably a short axon (aspiny II). A realistic interpretation of neurophysiologic data on the neostriatum must take into account all cell types instead of the current view of considering it as a pool of interneurons with few output cells.

Animals

Synapses between interneurons in the lateral geniculate nucleus of monkeys.

Electron microscopic examination of the monkey lateral geniculate nucleus, pars dorsalis (LGNd) reveals the occurrence of synaptic contacts between profiles belonging to interneurons (I-cells). Almost all combinations are observed, namely, axodendritic, dendrodendritic, dendrosomatic and somatodendritic, the most frequent being the dendrodentritic synapses between the presynaptic dendrites characteristic of I-cells. Quantitative analysis of 5 samples, each consisting of 200 mum2 of net LGNd neuropil, shows that presynaptic membrane specializations present in I-cell axonal and dendritic elements amount to a mean of 3.73 mum or 8.16% of the surface of such profiles. Only 61% of this extent is in contact with principal cells (P-cells), and an unexpectedly high 39% engages other I-cell profiles. A tentative segregation of axonal and dendritic endings revealed the following significant mean differences: dendritic terminals are more numerous and larger; axonal profiles have more of their surface occupied by synaptic sites and each contact is longer. Findings suggest the existence of a network of interconnected interneurons which are presumably inhibitory in nature. Such an arrangement can provice a certain measure of anisotropic disinhibition which may be responsible for specific transformations occurring in the LGNd depending upon the size and velocity of the stimulus as well as of the degree of synchronicity of temporal patterns.

Animals

A comparison between two types of visually-evoked nystagmus in the monkey.

Similarities between optokinetic nystagmus (O.K.N.) and flicker-induced nystagmus (F.I.N.) include: response buildup and occurrence during the entire period of stimulation; absence of habituation; after-nystagmus in the same direction, occasional after-after-nystagmus to the opposite side; frequency spectrum, peak frequency and existence of lower and upper frequency thresholds. Phenomena are different in that for O.K.N. the stimulus is in motion; binocular and monocular stimulation are effective; direction is determined by direction of motion; unidirectionality is absent; there is minimal influence of background illumination, posture, labyrinthine receptors, and section of crossed optic fibers. For F.I.N. the stimulus is stationary; the response is elicited only by monocular stimulation; the direction is determined by the stimulated eye; there is exclusive unidirectionality; it is abolished by background illumination, optic chiasm section and bilateral labyrinthectomy; it is strongly influenced by posture. This comparison suggests that O.K.N. and F.I.N. are separate responses and that the effective stimulus for F.I.N. may activate selectively the crossed optic fibers.

Animals

Postnatal differentiation of "presynaptic dendrites" in the lateral geniculate nucleus of the rhesus monkey.

The most characteristic synaptic arrangement in the LGN is the triadic unit, in which a retinal terminal is presynaptic to a principal cell (P cell) and to a Golgi interneuron (I cell) dendrite, which contains synaptic vesicles and is in turn presynaptic to the same P-cell element. The ontogenetic differentiation of these "presynaptic dendrites" was studied in monkey LGN by standard and quantitative electron microscopy. The dendrites and axonal arborization of I cells are well developed in the newborn monkey. Scattered synaptic vesicles are present in the dendrites, but these profiles exhibit only postsynaptic sites. The dendrodendritic synapse of the triadic arrangement is missing, although contacts between P-cell and I-cell dendrites can be observed. Conversely, the I-cell axons in the newborn establish numerous synapses with dendrites and perikarya of P cells. At about 2 weeks of age, presynaptic sites appear in the I-cell dendrites, resulting in the formation of synaptic triads. Parallel to the development of "axonal" properties in the dendrites, the number of true I-cell axonal profiles decreases sharply. These transformations become progressively more frequent with age, and beyond 8 weeks the LGN ultraarchitectonics approaches that of the mature animal. The percentage of the surface of interneuron processes occupied by presynaptic sites is similar at all developmental stages at about the 2.6% level. The relative contribution of presynaptic dendrites and of axons changes, however, so that the actual length of contacts in the mature monkey is only one-half that of the newborn for the axonal sites, and over 50 times longer for the dendritic sites. The correlation of these findings with electrophysiologic and behavioral references suggests that some but not all axonal functions may be taken over by the dendrites, that the possible inhibitory phasing of P-cell discharge would appear only after the second postnatal week, and that the triadic arrangement may not be indispensable for brightness or total luminous flux discrimination but could be required for more complex forms of visually guided behavior.

Animals