This chapter summarizes K. S. Lashley's viewpoints on the mechanism of vision. A major group of papers in The Mechanism of Vision series have as a central theme the testing of rats with destruction of the visual cortical areas. Lashley found that rats with practically complete striatectomy jumped readily and oriented to visual targets. The jumping accuracy of Lashley's destriated rats can be interpreted as relatively preserved visual space localization. Although this ability was not discovered in similarly operated monkeys, there were indications from work on one such animal with incomplete ablations that it could localize visual events in space. The last subject covered in The Mechanism of Vision is strictly anatomical and involves studies on the structure and image-forming power of the eye, as well as on the sites of termination of retinal fibers and the cortical projections of the lateral geniculate nucleus.

DYT1 dystonia is a severe form of young-onset dystonia caused by a mutation in the gene that encodes for the protein torsinA, which is thought to play a role in protein transport and degradation. We describe, for the first time to our knowledge, perinuclear inclusion bodies in the midbrain reticular formation and periaqueductal gray in four clinically documented and genetically confirmed DYT1 patients but not in controls. The inclusions were located within cholinergic and other neurons in the pedunculopontine nucleus, cuneiform nucleus, and griseum centrale mesencephali and stained positively for ubiquitin, torsinA, and the nuclear envelope protein lamin A/C. No evidence of inclusion body formation was detected in the substantia nigra pars compacta, striatum, hippocampus, or selected regions of the cerebral cortex. We also noted tau/ubiquitin-immunoreactive aggregates in pigmented neurons of the substantia nigra pars compacta and locus coeruleus in all four DYT1 dystonia cases, but not in controls. This study supports the notion that DYT1 dystonia is associated with impaired protein handling and the nuclear envelope. The role of the pedunculopontine and cuneiform nuclei, and related brainstem brainstem structures, in mediating motor activity and controlling muscle tone suggests that alterations in these structures could underlie the pathophysiology of DYT1 dystonia [corrected]

The chemical identification of neurons containing various neuroactive substances and calcium-binding proteins, together with modern tracing methods, confirm to a great extent Cajal's views on the target selectivity of particular cell types in various regions. The hippocampal efferents taking the fimbria route to reach the septum correspond to axons of pyramidal cells of the regio inferior (∼CA3-4), whereas those of the regio superior (∼CAl-2) have both, collateral and terminal branches ramifying in the plexi of the strata oriens, radiatum and lacunosum. Chandelier cells are immunoreactive to parvalbumin further characterized this singular short axon cell, in fact, the only type that escaped Cajal's observational powers. Concerning the intrinsic functional polarization of the neuron, Cajal's ideas, as in most instances, evolved in trying to incorporate his ever-increasing amount of observations. Thus, the so-called “law of dynamic polarization” gave way to the law of axipetal polarization, which included the possibility of propagation of the nerve impulse from the soma to the dendrite, as it occurs in the case of the axon originating from a dendrite at a considerable distance from the soma.

Journal of Comparative NeurologyVolume 356, Issue 2 p. 165-165 Article János Szentágothai (1912-1994): A personal tribute Tauba Pasik, Tauba Pasik Department of Neurology, Mount Sinai School of Medicine, 1 Gustave Levy Place, New York, NY 10029Search for more papers by this authorPedro Pasik, Pedro Pasik Department of Neurology, Mount Sinai School of Medicine, 1 Gustave Levy Place, New York, NY 10029Search for more papers by this author Tauba Pasik, Tauba Pasik Department of Neurology, Mount Sinai School of Medicine, 1 Gustave Levy Place, New York, NY 10029Search for more papers by this authorPedro Pasik, Pedro Pasik Department of Neurology, Mount Sinai School of Medicine, 1 Gustave Levy Place, New York, NY 10029Search for more papers by this author First published: 29 May 1995 https://doi.org/10.1002/cne.903560202Citations: 1AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat No abstract is available for this article.Citing Literature Volume356, Issue229 May 1995Pages 165-165 RelatedInformation

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.

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.

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.

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.

The previous chapter covered our survey of the literature on the neostriatum. The present one completes the review of the other components of the basal ganglia system. A list of abbreviations can be found at the beginning of the preceding article.

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 affnity. 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.

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.

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.

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.