bluuebunny/crossref_metadata_2025 huggingface dataset:
Short and long term changes in tyrosine hydroxylase activity in rat brain after subtotal destruction of central noradrenergic neurons
Authors: Acheson AL , Zigmond MJ
Published: March 2018

The administration of 6-hydroxydopamine into the cerebroventricles of the rat produced a rapid and permanent decrease of norepinephrine in hippocampus due to an apparent degeneration of central catecholaminergic nerve terminals. The decrease in norepinephrine levels was accompanied by a decrease in the activity of the rate- limiting biosynthetic enzyme, tyrosine hydroxylase. However, the decrease in enzyme activity was less pronounced than the decrease in norepinephrine levels, resulting in an increase in the ratio of tyrosine hydroxylase activity to norepinephrine content. This relative increase in enzyme activity was shown to result from two processes. Within 36 hr after the lesion, the apparent Vmax had decreased in parallel to the norepinephrine loss. However, there was an apparent activation of the remaining enzyme molecules. This activation was only detectable in the presence of subsaturating cofactor concentrations and at a pH above the pH optimum. The activation resembled that produced in control samples by in vitro adenosine 3′:5′-monophosphate-dependent protein-phosphorylating conditions, and incubation under these conditions had no further effect on enzyme activity. The activation was followed by a gradual increase in the apparent Vmax of tyrosine hydroxylase toward control values. This increase was preceded by a 2-fold rise in the amount of enzyme present in the region of the locus coeruleus, an area rich in noradrenergic cell bodies. The time course of the increased Vmax in terminal fields appeared to be related to their proximity to the locus coeruleus, since it was more rapid for cerebellum (peak activity, 7 days) than for hippocampus (21 days) and probably represented a 3- to 4-fold increase in the amount of tyrosine hydroxylase per residual terminal. The increase in the Vmax was accompanied by a return to a basal activation state of the enzyme molecules and a restoration of the ability of in vitro protein- phosphorylating conditions to increase enzyme activity. These short and long term alterations in tyrosine hydroxylase activity after 6- hydroxydopamine treatment may represent adaptive responses to the lesion.
Evidence for collateral projections by neurons in Ammon's horn, the dentate gyrus, and the subiculum: a multiple retrograde labeling study in the rat
Authors: Swanson LW , Sawchenko PE , Cowan WM
Published: March 2018

Although it has been recognized for some years that each cytoarchitectonic field of Ammon's horn and the subiculum gives rise to a specific pattern of cortical and subcortical projections, it has not been clear whether these various projections arise from different populations of neurons within each field or whether they arise as collaterals from an essentially homogeneous population of cells. We have examined this problem, and the related issue of the origin of the commissural and ipsilateral associational projections of the dentate gyrus, by injecting retrogradely transported fluorescent dyes into two or more of the relevant projection fields in adult rats and subsequently examining the brains for doubly or triply labeled neurons. It is clear from these experiments that at least two of the known efferent projections of field CA1 (to the septum and to the entorhinal cortex) arise from the same pyramidal neurons and also that the commissural, ipsilateral associational, septal, and subicular projections of the other major field of Ammon's horn--field CA3-- similarly are due to collaterals. Double-labeling experiments also indicate that at least 80% of the cells in the deep hilar region of the dentate gyrus give rise to both an ipsilateral (associational) and a crossed (or commissural) projection to the dentate granule cells. In contrast, the projection neurons in the dorsal part of the subiculum form a quite heterogeneous population; cells that project to both the septum and the entorhinal area are intermingled with others that project to one or the other area but not to both. The cortical and cortico-subcortical connections of the hippocampal formation thus appear to be quite different from those of the neo-cortex, and the existence of such an extensive system of collateral projections clearly has important consequences for studies of the development of the hippocampus and of its response to selective deafferentation.
Cerebral compensation for chronic noradrenergic denervation induced by locus ceruleus lesion: recovery of receptor binding, isoproterenol- induced adenylate cyclase activity, and oxidative metabolism
Authors: Harik SI , Duckrow RB , LaManna JC , Rosenthal M , Sharma VK , Banerjee SP
Published: March 2018

The long term effects of specific noradrenergic denervation of rat cerebral cortex were considered in parallel studies of in vitro noradrenergic receptor binding and isoproterenol-induced adenosine 3′:5′-monophosphate (cycle AMP) generation and of in vivo oxidative metabolism. Noradrenergic denervation was achieved by the local, unilateral injection of 6-hydroxydopamine into the locus ceruleus. Cerebral noradrenaline remained depleted throughout the 8-week duration of the study. Ligand-binding assays showed increased beta-adrenergic receptors 2 weeks after locus ceruleus lesion with recovery occurring by 4 weeks. There were no changes in alpha 1-adrenergic receptors. Isoproterenol-induced cyclic AMP generation increased at 2 weeks after lesion but recovered at 8 weeks. Dual wavelength reflection spectrophotometric measurements of cytochrome oxidase reduction/oxidation and local blood volume shifts, provoked in situ by direct cortical stimulation, also demonstrated abnormalities at 2 weeks with recovery by 4 weeks after lesion. Thus, in vivo and in vitro changes after locus ceruleus lesion are reversible and the time course of these changes is related temporally. These data suggest that cerebral cortex has adaptive capabilities which are activated to compensate for prolonged noradrenaline depletion. We also speculate that there may be a causal relationship between the in vitro and in vivo parameters studied.
Isolated identified Aplysia neurons in cell culture
Authors: Dagan D , Levitan IB
Published: March 2018

Methods have been developed for primary culture of large identified Aplysia neurons. Aplysia ganglia were treated with neutral protease to soften the connective tissue sheath. Individual neurons were isolated either by manipulation with tungsten needles or by tying off their axons with fine nylon filament and were immobilized in a chick plasma clot or a solution of methylcellulose. Somata up to approximately 300 micrometers in diameter extended long processes within several hours in culture. A single neuron produced as many as 10 processes which could grow at different rates. Intracellular recordings showed spontaneous and evoked action potentials in neurons cultured for up to 6 weeks. Electrical synapses formed between pairs of neurons in culture. In several culture dishes containing neurons from buccal ganglia, electrical coupling was observed between 90% of the cell pairs tested. This primary culture system currently is being used to compare the electrical and biochemical properties of neuronal processes with those of cell bodies and to study the conditions necessary for process regeneration and synapse formation between isolated identified neurons.
The growth and organization of the optic nerve and tract in juvenile and adult goldfish
Authors: Easter SS , Rusoff AC , Kish PE
Published: March 2018

The optic nerves, tracts, and tecta of goldfish, 1 to 5 years old, have been studied anatomically using light and electron microscopy, horseradish peroxidase (HRP), and tritiated proline radioautography. The aims were to document an earlier inference that fibers are added to the nerve continually and to describe the growth and organization of the pathway. (1) The numbers of optic fibers were counted in electron micrographs of the nerve. There were about 120,000, 165,000 and 180,000 in 1-, 3-, and 5-year-old fish, respectively. (2) In young fish, there are a few thousand nonmyelinated fibers which exit the retina together and cluster together in the nerve and tract. When the axons of only the newest (peripheral) ganglion cells were cut intraretinally, fibers in and around the bundles of nonmyelinated fibers degenerated. The nonmyelinated fibers are, therefore, the new ones. (3) Fibers from ventral or dorsal hemiretinas were backfilled selectively with HRP introduced into one of the brachia of the optic tract. Behind the optic papilla, where the cross-section of the optic nerve was trapezoidal, the new fibers were found in a strip along the narrow base of the two flanking zones. Closer to the brain, the fibers from the two hemiretinas intermingled before being segregated again at the origin of the brachia. (4) Small groups of ganglion cells were labeled by intraretinal injection of HRP and their fibers were traced in sections of the nerve and tract. The labeled fibers were clustered, but the positions of the fibers in the cross-section of the nerve were defined less precisely than the positions of the somata in the retina. (5) Hemisection of the nerve in the orbit, followed by intraocular injection of tritiated proline, produced radioautographs with an unlabeled annular zone of tectum. Since the retina projects topographically to the tectum, the severed fibers must have originated from an annular region of the retina. We infer that new fibers are added to the nerve continually and that the retinal origins of fibers are correlated with their positions in the cross-section of the nerve. These rules of order change with distance from the retina; the strict order at the optic papilla changes gradually to an equally strict but different, order at the level of the brachia.
Mitosis of radial glial cells in the optic tectum of adult goldfish
Authors: Stevenson JA , Yoon MG
Published: March 2018

A class of tectal cells whose mitotic activity is enhanced by optic nerve regeneration in adult goldfish has been identified as radial neuroglia. These mitotic glial cells are morphologically distinct cells with prominent radial processes which extend through the entire depth of the tectal layers. The radial glia incorporate exogenous [3H]thymidine ([3H]TdR) into DNA as early as 2 hr after systemic injection. The plane of cell division for the mitotic radial glia is always aligned to the equator of the cell body, perpendicular to the direction of the radial process. In a few cases, radially adjacent pairs of labeled daughter radial glial cells are observed as early as 12 hr and also as late as 51 days after [3H]TdR injection. In other cases, however, only one labeled daughter radial glial cell is identified, and the other daughter cell cannot be traced. These observations suggest that radial glial cells of the adult goldfish tectum can be induced (presumably by mitogenic effects of regenerating optic nerve fibers) to undergo mitosis.
Rohon-Beard neurons arise from a substitute ancestral cell after removal of the cell from which they normally arise in the 16-cell frog embryo
Authors: Jacobson M
Published: March 2018

In 16-cell Xenopus embryos, horseradish peroxidase (HRP) was injected into blastomere D1.2 on one side. No Rohon-Beard neurons originated from D1.2 in either of the two patterns of cleavage that were studied (Jacobson, M. (1981) J. Neurosci. 1: 918–922). In other embryos, after injection of HRP into D1.2, the neighboring ventral blastomere V1.2, from which 68 to 90% of Rohon-Beard neurons normally originate, was removed. In the cases that developed normally to larval stages 32 to 34, the number and sizes of Rohon-Beard neurons were normal, but 14.9 to 73.9% of Rohon-Beard neurons were labeled, showing that they originated from the injected blastomere D1.2. Labeling also occurred in cells of the spinal dorsal root ganglia that normally descend from V1.2 but not from D1.2. This proves that individual blastomeres at the 16- cell stage are not committed to form specific types of neurons or restricted parts of the central nervous system.
The visual claustrum of the cat. II. The visual field map
Authors: LeVay S , Sherk H
Published: March 2018

Physiological and anatomical methods were used to study the representation of the visual field in the cat's dorsocaudal claustrum. In one set of experiments, the visual receptive fields of claustral neurons were plotted in multiple electrode penetrations. In another set of experiments, the termination of the corticoclaustral pathway was examined autoradiographically after the injection of [3H]proline at retinotopically defined sites in the visual cortex. Results obtained by the two methods were in close agreement. The claustrum was found to contain a single, orderly map of the contralateral hemifield and a small part of the ipsilateral field. High elevations are represented caudally and ventrally, low elevations rostrally and dorsally. The surface of the claustrum represents the periphery of the visual field, while the vertical meridian lies more ventrally, where the visual claustrum abuts the non-visual part of the nucleus. Visual field lines (isoazimuths or isoelevations) are represented as planes in the claustrum. The map is unusual in that isoazimuth planes are strongly curved and nested within each other, with peripheral ones enclosing those closer to the vertical meridian. This arrangement permits an expanded representation of the periphery compared with what is seen in visual cortex. The inputs from areas 17, 18, 19, 21a, and PMLS (posteromedial lateral suprasylvian area) are convergent, each projection retinotopically to the entirety of the claustral map.
The visual claustrum of the cat. III. Receptive field properties
Authors: Sherk H , LeVay S
Published: March 2018

The visual response properties of cells in the cat's dorsocaudal claustrum were studied physiologically. Quantitative observations were made of 55 cells, and qualitative observations were made on 228 others. The claustral cells formed a physiologically homogeneous population. The overwhelming majority were orientation selective, and most also showed a striking preference for long stimuli, their responses summating up to lengths of 40 degrees or more. Moving stimuli were always much more effective than stationary ones. In other respects, claustral cells were tolerant of wide variation in stimulus features. Their responses were about equally brisk to either direction of movement of a properly oriented stimulus, and the velocity of movement was likewise not critical. They appeared not to summate across the dimension of their receptive fields orthogonal to the preferred orientation so that narrow or broad slits, or edges, evoked similar responses. Dark slits on light backgrounds were as effective as light slits on dark backgrounds. Finally, a large majority of cells were driven equally well by either eye. These properties of claustral cells differ in several respects from those of their principal targets, cells in layer IV of visual cortex.
The action of nerve growth factor and dibutyryl adenosine cyclic 3':5'- monophosphate on rat pheochromocytoma reveals distinct stages in the mechanisms underlying neurite outgrowth
Authors: Gunning PW , Letourneau PC , Landreth GE , Shooter EM
Published: March 2018

The clonal rat pheochromocytoma, PC12, responds to nerve growth factor (NGF) and dibutyryl adenosine cyclic 3′:5′monophosphate (dbc AMP) by the elevation of cellular protein and RNA levels in all three parameters that are additive or greater than the sum of those caused by either agent alone, indicating that the mechanisms by which the two agents act to produce these changes are distinct. The concentration of dbcAMP required for half-maximal stimulation of these changes is also different for each, while NGF is active in all instances at 10(-11) M. PC12 cells initially generate neurites slowly in response to NGF and, at the same time, develop the capacity to regenerate neurites rapidly, a process termed priming. The cells, however, are not primed by dbcAMP nor does it influence the ability of NGF to prime them. Time lapse cinematography demonstrates that both NGF and dbcAMP each have unique effects on cellular morphology. The latter produces' rapid, unstable neurite initiation but does not promote sustained neurite extension. In contrast, NGF has immediate effects at the cell surface with no neurite initiation but later produces sustained neurite outgrowth. Utilizing dbcAMP, it is possible to dissect four morphological response of PC12 cells to NGF. Three of these may be mechanistically closely tied to occupancy of the NGF plasma membrane receptor.
Serotonin autoreceptors on dorsal raphe neurons: structure-activity relationships of tryptamine analogs
Authors: Rogawaski MA , Aghajanian GK
Published: March 2018

A series of indole-ethylamines were tested for their ability to suppress the spontaneous firing of single dorsal raphe serotonergic neurons in the rat. The compounds were all derivatives of either tryptamine or N,N-dimethyltryptamine possessing hydroxy or methoxy substituents on the benzene ring portion of the indole nucleus. Their activity was assessed using quantitative microiontophoresis or following systemic (intravenous) administration. The serotonin autoreceptor or so-called “S2 receptor” mediating the inhibition of raphe serotonergic neurons was found to exhibit a high degree of structural specificity among the closely related tryptamine analogs. The following structure-activity rules were demonstrated: (1) for either hydroxy or methoxy derivatives, the relative favorability of the ring positions conforms to the series 5 much greater than 4 greater than 6; (2) methoxy derivatives are more sensitive to a shift of the ring substituent from the 5- to the 4- or 6-positions than are hydroxy compounds; and (3) activity is enhanced by N,N-dimethylation. Furthermore, addition of a methyl group at the 7-position of 5-methoxy- N,N-dimethyltryptamine markedly reduces the activity of this potent agonist. Of the radioligands which label brain serotonin receptors, the pharmacological characteristics of D-[3H]lysergic acid diethylamide binding best correspond to those displayed by the S2 receptor as determined in the present physiological analysis, although sufficient data are not yet available to make a complete comparison.
Action of a trophic factor(s) from rabbit corneal epithelial culture on dissociated trigeminal neurons
Authors: Chan KY , Haschke RH
Published: March 2018

Cultured corneal epithelial cells release a factor(s) that stimulates trigeminal neurons to form neurites in vitro. To characterize this trophic effect, conditioned media (serum free, supplemented) from cultures for corneal epithelium, stromal fibroblasts, and endothelium were studied further. Only epithelial conditioned medium (PCM) prolonged neuronal survival and induced neurite outgrowth. This trophic influence peaked after 2 to 3 days and gradually declined thereafter during a week when the medium was not renewed. Using a bioassay to score the percentage of initially viable neurons that extended neurites, it was found that the trophic effect of PCM was proportional to the conditioned medium concentration and to the cell density of the epithelial culture used for the conditioning. Maximum activity in PCM was correlated with confluency of the epithelial culture. Experiments using antiserum to nerve growth factor (NGF) and purified antibody to cold-insoluble globulin (CIG) indicated that the tropic effect of PCM was not derived from NGF or CIG. The trophic activity of PCM was abolished totally by heat or trypsin treatment but was not affected by collagenase. Although a fraction of the trophic activity was associated with the substratum after adsorption of PCM, this and other evidence did not suggest that the primary action of PCM was to enhance neuronal adhesion.
Effects of damage to the suprachiasmatic area of the anterior hypothalamus on the daily melatonin and cortisol rhythms in the rhesus monkey
Authors: Reppert SM , Perlow MJ , Ungerleider LG , Mishkin M , Tamarkin L , Orloff DG , Hoffman HJ , Klein DC
Published: March 2018

The effects of lesions of the suprachiasmatic nucleus (SCN) on the circadian rhythms in melatonin and cortisol were examined in the rhesus monkey. The concentrations of the two hormones were monitored in cerebrospinal fluid (CSF) withdrawn from two sham-operated animals, two animals with complete bilateral SCN lesions, and two animals with partial SCN damage at 4 and 8 months after surgery. In the sham- operated animals, as in the intact animal, the daily melatonin rhythm was entrained to the daily light-dark cycle, was suppressed in constant light, and persisted in constant darkness. In contrast, neither animal with complete SCN ablation exhibited a daily pattern of CSF melatonin in diurnal lighting at 4 months after surgery nor were their melatonin levels at constant low values. Furthermore, CSF melatonin concentrations were not suppressed in either animal by constant light. Surprisingly, at 8 months after surgery, spectral analysis revealed a 24-hr component to the melatonin patterns for each animal with complete SCN ablation in both diurnal lighting and constant darkness. The two animals with partial SCN damage exhibited a daily melatonin rhythm in diurnal lighting, but constant light did not suppress CSF melatonin concentrations consistently. Daily rhythms persisted in both for a 6 1/2-d period of study in constant darkness. In contrast to the alterations in the melatonin rhythm after SCN damage, there was no apparent effect of either partial or complete SCN ablation on the daily CSF cortisol rhythm. These data indicate that, in the rhesus monkey, the SCN is important for the generation, photic entrainment, and photic suppression of the melatonin rhythm. However, circadian oscillators located outside of the SCN region may control the normal daily cortisol rhythm and perhaps the melatonin rhythm in the absence of the SCN.
Extracellular current flow and the site of transduction by vertebrate hair cells
Authors: Hudspeth AJ
Published: March 2018

The transduction process of a vertebrate hair cell commences with the application of mechanical stimuli to the hair bundle, a cluster microvillous stereocilia and single axonemal kinocilium. In an effort to determine where within the hair bundle transduction occurs, I have measured extracellular potentials around the hair bundles of mechanically stimulated hair cells from the bullfrog's sacculus. Stimulus-dependent signals up to 17 microV in peak-to-peak amplitude have been found. These appear to be due to the flow of transduction current on the basis of their amplitude, phase, dependence on stimulus size and orientation, proportionality to membrane potential, and sensitivity to an ototoxic antibiotic. The responses are consistently larger near the top of the hair bundle than at its base, suggesting that the transduction apparatus lies at or near the distal ends of the stereocilia.
Electrophysiological and pharmacological characteristics of the serotonin response on a vertebrate neuronal somatic cell hybrid
Authors: Freschi JE , Shain WG
Published: March 2018

We studied the effects of 5-hydroxytryptamine (5-HT, serotonin) on the vertebrate neuronal somatic cell hybrid TCX11. We compared electrophysiological and pharmacological properties of the 5-HT response to those of the dopamine (DA) response. The cells developed delayed rectification and the ability to generate action potentials. Both 5-HT and DA caused graded depolarizations associated with increases in membrane conductance. The cells, however, were 10 to 100 times more sensitive to 5-HT than to DA. Responses to the amines desensitized during sequential or continuous application, and each neurotransmitter could desensitize the cell to a subsequent dose of the other neurotransmitter (cross-desensitization). Reversal potentials for both amines ranged from 0 to 15 mV from cell to cell, but on any given cell, the reversal potentials for 5-HT and DA were equal. We applied a variety of drugs, including classical DA and 5-HT antagonists, and found no drug that blocked the response to one amine without a similar inhibition of the response to the other amine. We conclude that, on the hybrid TCX11, there is a receptor that mediates a depolarizing response with a conductance increase after interaction with 5-HT and DA. Our data suggest that the receptor is best classified as a serotonin receptor.
Substance P-like immunoreactivity in neurons in dissociated cell cultures of mammalian spinal cord and dorsal root ganglia
Authors: Neale EA , Matthew E , Zimmerman EA , Nelson PG
Published: March 2018

Dissociated cell cultures prepared from fetal mouse spinal cords and dorsal root ganglia were stained for endogenous substance P using the peroxidase-antiperoxidase technique. Substance P-like immunoreactivity was localized within a small percentage of rounded or multipolar neuronal somata and in varicose processes. The substance P-positive multipolar neurons were derived from spinal cord, while the small rounded neurons were possibly of spinal cord and/or sensory ganglion origin. Large dorsal root ganglion neurons were unreactive. These results are consistent with in vivo findings and indicate the feasibility of electrophysiologic studies in culture to analyze the synaptic connections between substance P neurons and their target cells.
Formation of photoreceptors in larval and adult goldfish
Authors: Johns PR
Published: March 2018

Histogenesis of the photoreceptor layer in the retina of goldfish was studied morphometrically and with thymidine radioautography at the light microscopic level. At hatching, the photoreceptor layer is poorly differentiated. The cells in the outer nuclear layer that are postmitotic' at hatching differentiate into cones. Two to 3 days after hatching, rod nuclei appear in the outer nuclear layer , and rods begin to differentiate. Rods and rod nuclei accumulate across the retina during larval and juvenile life. It is proposed that rods are generated in the outer nuclear layer by dividing progenitor cells that may be analogous to subventricular cells. Rod progenitors appear to derive from clusters of undifferentiated cells in the inner nuclear layer, which are called neurogenic clusters. Some of these cells apparently migrate across the outer plexiform layer from the inner to the outer nuclear layer and then divide to produce rods. The ontogenetic sequence of photoreceptor development in the larval retina is recapitulated continuously in the circumferential growth zone at the margin of the juvenile and adult retina. New rods continue to be inserted, but at a slower rate, throughout the adult retina; this may explain how the density of rods is maintained constant despite the expansion of the retinal surface that accompanies growth of the eye.
Modulation by estradiol of serotonin receptors in brain
Authors: Biegon A , McEwen BS
Published: March 2018

Estrogens were found to exert a biphasic effect on the density of serotonin receptors in the female rat brain: an acute reduction in serotonin receptor density throughout the brain is followed 48 to 72 hr later by a selective increase in those brain regions known to contain estrogen receptors--hypothalamus, preoptic area, and amygdala. The acute reduction in serotonin receptor density can be mimicked by estradiol in vitro. We conclude that estradiol may have a fast, direct effect on brain membranes to modify serotonin receptor availability, while exerting a slow effect on the same receptors through an interaction with intracellular estrogen receptors in those brain regions that contain them. The observation that female sex hormones are involved in the regulation of serotonin receptors may have important implications in the understanding of female sexual behavior in the female rat and in the understanding of hormone-linked emotional disturbances in women.
The pattern of interhemispheric connections and its relationship to extrastriate visual areas in the macaque monkey
Authors: Van Essen DC , Newsome WT , Bixby JL
Published: March 2018

The distribution of interhemispheric connections was studied in extrastriate visual cortex of the macaque monkey. Callosal fiber terminations were identified by staining for anterograde degeneration following transection of the splenium of the corpus callosum. Retrogradely labeled cell bodies of callosal projection neurons were identified histochemically following application of horseradish peroxidase to the cut surface of the callosum. Results were displayed on unfolded, two-dimensional representations of the cortex, which permitted spatial and topological relationships between callosal recipient and callosal free cortical regions to be discerned readily. The overall pattern of callosal inputs to visual cortex can be subdivided into nine callosal recipient zones which surround seven callosal free regions in the occipital, temporal, and parietal lobes. This pattern provides reliable and useful landmarks for identifying the borders of at least five topographically organized extrastriate visual areas. There is a pronounced dorsoventral asymmetry in callosal projections, not recognized in previous studies, which reflects an asymmetry in the organization of visual areas in dorsal versus ventral halves of the occipital lobe. The pattern of callosal fiber terminations is mirrored by a very similar distribution of callosal projection neurons. There are significant regional differences in the laminar distribution of callosal projection cells, and these differences may reflect functionally distinct cortical subdivisions. A considerable degree of individual variability was found in the relationship of callosal connections to gyral and sulcal landmarks as well as in the fine structure of individual callosal recipient strips, suggesting that each animal has a unique “callosal fingerprint.” These findings emphasize the usefulness of the callosal pathway in elucidating the functional organization of extrastriate visual cortex.
Coordination of arm and wrist motion during a reaching task
Authors: Lacquaniti F , Soechting JF
Published: March 2018

An analysis of arm movements involving forward projection of the hand in order to reach for and grasp a target at different orientations is presented. The reaching movements required shoulder flexion, elbow extension, and wrist pronation or supination. The relation between elbow and shoulder instantaneous angular position proved to be consistent from trial to trial of each task, independent of movement speed. Further, this relation was not influenced by the presence or absence of a concomitant wrist rotation. During the deceleratory phase of the movement, the slope of elbow angular velocity to shoulder angular velocity was constant and independent of target orientation. Wrist motion was instead highly variable in timing, course, and duration. Supinatory movements tended to be fractionated. On average, the duration of wrist movements was shorter than that of shoulder and elbow motions. The pattern of biceps EMG activity during supinatory and pronatory movements was different. Since motion at the shoulder and elbow was virtually identical in the two cases, net flexor torque at the elbow was also little different. It is concluded that other elbow flexors and extensors also exhibit a task-dependent patterning of activity so as to produce the same net torque. The results are discussed in the context of the internal constraints present during the movements that we examined. These constraints are the inertial coupling between shoulder and elbow motion and those which derive from the bifunctional nature of many of the muscles participating in the movement.
Temporal patterns of somatostatin immunoreactivity in the cerebrospinal fluid of the rhesus monkey: effect of environmental lighting
Authors: Arnold MA , Reppert SM , Rorstad OP , Sagar SM , Keutmann HT , Perlow MJ , Martin JB
Published: March 2018

A rabbit antiserum to somatostatin was used to develop radioimmunoassay methods for measuring somatostatin in monkey cerebrospinal fluid (CSF). By gel permeation chromatography, at least five molecular weight forms of immunoreactive somatostatin (IRS) were identified in monkey CSF; two of these species co-migrated with either synthetic somatostatin-14 or somatostatin-28. The 24-hr profile of CSF somatostatin immunoreactivity was obtained from five monkeys during diurnal lighting, constant light, and constant darkness. During diurnal lighting, all five monkeys had a clear ultradian component in CSF IRS of 4 to 5 hr duration; this pattern was not affected significantly by constant light or dark. In addition, there of the five monkeys exposed to diurnal lighting showed a diurnal rhythm in CSF IRS, with higher hormone levels during darkness. In some animals, this diurnal rhythm also could be demonstrated during constant light or dark.
A primary acoustic startle circuit: lesion and stimulation studies
Authors: Davis M , Gendelman DS , Tischler MD , Gendelman PM
Published: March 2018

The latency of the acoustic startle reflex in the rat is 8 msec, measured from tone onset to the beginning of the electromyographic response in the hindleg. This extremely short latency indicates that only a few synapses could be involved in some primary acoustic startle circuit. Acoustic startle is being used as a model system for studying habituation, sensitization, prepulse inhibition, classical conditioning, fear or anxiety, and drug effects on behavior. The present study attempted to delineate a short latency acoustic startle circuit, since this would provide critical information for further study in all of these areas. Bilateral lesions of the ventral cochlear nucleus, which receives the primary auditory input, abolish acoustic startle. Electrical, single pulse stimulation of the ventral cochlear nucleus elicits startle-like responses with a latency of about 7 msec. Bilateral lesions of the dorsal and ventral nuclei of the lateral lemniscus, which receive direct input from the ventral cochlear nuclei, abolish acoustic startle. Electrical stimulation of these nuclei elicits startle-like responses with a latency of about 6 msec. Bilateral lesions of ventral regions of the nucleus reticularis pontis caudalis, which contain cell bodies that give rise to the reticulospinal tract, abolish acoustic startle. Electrical stimulation of these points elicits startle-like responses with a latency of about 5 msec. Reaction product from horseradish peroxidase iontophoresed into this area is found in the nuclei of the lateral lemniscus. In contrast, lesions of the dorsal cochlear nuclei, vestibular nuclei, nucleus reticularis pontis oralis, nucleus reticularis gigantocellularis, and dorsal regions of the nucleus reticularis pontis caudalis fail to abolish acoustic startle. Also, “startle” cannot be elicited electrically from these areas. The data suggest that a primary acoustic startle circuit in the rat consists of auditory nerve, ventral cochlear nucleus, nuclei of the lateral lemniscus, nucleus reticularis pontis caudalis, spinal interneuron, lower motor neuron, and muscles. Hence, five synapses, plus the neuromuscular junction, are probably involved.
Appearance and distribution of neuronal cell surface and synaptic vesicle antigens in the developing rat superior cervical ganglion
Authors: Greif KF , Reichardt LF
Published: March 2018

Monoclonal antibodies directed against a neuronal cell surface heparan sulfate proteoglycan and against a synaptic vesicle protein were used to study the postnatal development of ganglionic neurons and synapses in the rat superior cervical ganglion. Antigen levels in developing ganglia were quantitated by radioimmune assays. Localization of antigens in adult and developing ganglia was carried out using peroxidase-antiperoxidase immunocytochemistry at the light microscopic level. Ultrastructural staining patterns in adult ganglia also were studied. The time course of antigen increases parallels those in previous reports on the accumulation of neurotransmitter enzymes within the ganglion. Both synaptic and surface antigens increase postnatally, with the most rapid changes occurring during the 2nd week. Antibodies stain adult tissue in patterns consistent with the expected distribution of antigens: antibodies directed against synaptic vesicles stain synaptic terminals and cell cytoplasm and those directed against surface proteoglycan stain the plasma membranes of neuronal cell bodies and processes. Variable staining of the cell cytoplasm also is observed. No apparent changes in antigen distribution are observed with the light microscope during development. Variations in the time course of the development of antigens associated with different portions of the proteoglycan molecule suggest that the intracellular processing of the molecule may vary during development.
Differential regulation of the mu-, delta-, and kappa-opiate receptor subtypes by guanyl nucleotides and metal ions
Authors: Pfeiffer A , Sadee W , Herz A
Published: March 2018

The effects of Na+, guanyl-5′-yl imidodiphosphate (Gpp(MH)p), and Mn2+ on the binding of dihydromorphine, ethylketocyclazocine, D-Ala2, D-Leu5- enkephalin, and diprenorphine to the opiate receptor were investigated. Three distinct binding sites, mu, delta, and kappa sites, were identified with the use of multiple tracer displacement curves. Moreover, this approach was used to determine the effects of Gpp (NH)p and metal ions on each individual binding site. At the mu and delta sites, Na+ and Gpp(NH)p each decreased and Mn2+ increased agonist binding affinities, with the exception of D-Ala2, D-Leu-enkephalin affinity which was not affected by Gpp(NH)p. None of these conditions markedly altered dihydromorphine and D-Ala2, Leu5-enkephalin binding to kappa sites, whereas the affinity of ethylke-tocyclazocine for kappa sites was decreased by Gpp(NH)p. Sodium ions lowered the capacity of mu sites and Gpp(NH)p reduced that of delta sites, while both agents increased the capacity of apparent kappa sites. These results demonstrate that each of the kinetically distinguishable binding sites is regulated differentially by metal ions and guanyl nucleotides. Simultaneous addition of Na+ and Gpp(NH)p greatly reduced the binding affinity of all three agonists at their respective high affinity sites (dihydromorphine at the mu site, D-Ala2, D-Leu5-enkephalin at the delta site, and ethylketocyclazocine at the kappa and mu sites). This result confirms previous observations that agonist binding is characterized by a large affinity reduction in the presence of both Na+ and guanyl nucleotides, and it extends this concept to each of the opiate receptor subtypes.
Localization of substance P-like and enkephalin-like immunoreactivity within preganglionic terminals of the avian ciliary ganglion: light and electron microscopy
Authors: Erichsen JT , Karten HJ , Eldred WD , Brecha NC
Published: March 2018

The avian ciliary ganglion receives its only recognized input from the nucleus of Edinger-Westphal. This is known to be a cholinergic input. In the present study, using fluorescein isothiocyanate and peroxidase- antiperoxidase immunohistochemical methods, substance P-like and enkephalin-like immunoreactivity has been found within preganglionic terminals of the avian ciliary ganglion. The ciliary ganglion is known to consist of two distinct cell populations: small choroid cells that project to the smooth muscle coat of the choroid and large ciliary neurons that send axons to both the iris and the ciliary body. Preganglionic terminals on choroid cells consist of small boutonal endings, whereas ciliary neurons receive a calyx-like cap ending around the hilus of the cell. Substance P-like and enkephalin-like immunoreactivity was localized to preganglionic axons and to both boutonal and calyx-like terminations upon cells of the ciliary ganglion. Electron microscopic studies of both substance P-like and enkephalin-like immunoreactive terminals revealed small clear core vesicles (approximately 58 nm in diameter) and two sizes of dense core vesicles (approximately 85 and approximately 119 nm in diameter). Immunoreactive staining was observed only in the smaller dense core vesicles. The unlabeled clear core vesicles were clustered at synaptic release sites, while the immunoreactive and larger unlabeled dense core vesicles usually were not near these synaptic specializations. These observations strongly imply that neuropeptides co-occur with acetylcholine in preganglionic axons of the ciliary ganglion.
The afferent and efferent callosal connections of retinotopically defined areas in cat cortex
Authors: Segraves MA , Rosenquist AC
Published: March 2018

We compared the callosal afferent and efferent connections of different retinotopic loci within a given visual cortical area as well as the connectivity patterns among similar retinotopic loci in different visual areas. Small injections (75 nl) of a mixture of horseradish peroxidase and [3H]leucine were made through a recording pipette at injection sites identified by retinotopic mapping. A small locus of cortex within a callosally connected region had precise reciprocal connections with the homotopic locus in the contralateral hemisphere. This small locus also was callosally connected with a variable number of heterotopic loci. Both reciprocal and nonreciprocal heterotopic callosal connections were found. Homotopic and heterotopic connections appeared to have a high degree of retinotopic fidelity. Precisely homotopic connections were present not only between locations on the vertical meridian representations at the left and right area 17/18 borders but also, for example, between mirror-symmetrical points on the peripheral horizontal meridian representation in the left and right posteromedial lateral suprasylvian areas. In several experiments, we found that both callosal neurons and terminals in the homotopic cortex were grouped into two to three distinct clusters ranging from 600 to 900 micrometers in width. Callosal neurons with homotopic connections were primarily pyramidal cells in lower layer III and upper layer IV. Outside of areas 17 and 18, there was a significant number of pyramidal and fusiform-shaped callosal neurons in layers V and VI. The majority of callosal terminals were located in layers II, III, and IV.
Blockade of retrograde axonal transport delays the onset of metabolic and morphologic changes induced by axotomy
Authors: Singer PA , Mehler S , Fernandez HL
Published: March 2018

Axotomy-induced increase in 2-deoxyglucose (2-DG) uptake by motor nuclei and neuronal chromatolytic changes were studied after subepineural injection of colchicine into the motor nerve. Hypoglossal nuclei of either cats or rats were axotomized bilaterally, while one of the nerves was injected with colchicine or saline proximal to the site of nerve transection and the other was left intact or injected with saline. Colchicine abolished or decreased the uptake of 2-DG by axotomized nuclei and delayed the onset of chromatolysis. The decrease in 2-DG uptake was observed in rat hypoglossal nuclei between 24 and 48 hr but not 5 days after drug treatment. In turn, a delay in the onset of chromatolysis was observed in cat hypoglossal nuclei at 14 days but not 30 days after treatment. Saline did not prevent chromatolysis nor the increased uptake of 2-DG. Colchicine injected intraneurally in intact preparations did not result in chromatolysis or in increased 2- DG uptake. Following colchicine injection, the drug remained localized near the site of injection and blocked retrograde axonal transport of horseradish peroxidase in the hypoglossal nerve. These findings suggest that the onset of chromatolysis and of the increase in 2-DG uptake after axotomy are partly dependent upon retrograde axonal transport.
Nerve growth factor-induced increase in saxitoxin binding to rat PC12 pheochromocytoma cells
Authors: Rudy B , Kirschenbaum B , Greene LA
Published: March 2018

The PC12 clone is a line of rat pheochromocytoma cells which undergoes neuronal differentiation in the presence of nerve growth factor (NGF) protein. In the absence of NGF, PC12 cells are electrically inexcitable, while after several weeks of NGF treatment, they develop sodium action potentials. The number and density of sodium channels on PC12 cells before and after treatment with NGF were estimated by measuring the binding of [3H]saxitoxin ([3H]STX). The data indicate that [3H]STX binding increases in the NGF-treated cells by 15- to 20- fold per cell, 3- to 10-fold per mg of protein, and an estimated 7-fold per unit area of membrane. The kinetic properties for [3H]STX binding are unchanged, however, by NGF treatment. A Hodgkin-Huxley analysis (Hodgkin, A. L., and A. F. Huxley (1952) J. Physiol. (Lond.) 117: 500– 544) suggests that the estimated density of sodium channels in NGF- untreated PC12 cells is sufficient to explain their lack of excitability. On the other hand, the estimated channel density on the NGF-treated cells (30 to 50/micrometers 2) is comparable to that in other excitable systems. Thus, the development of excitability in PC12 cells in response to NGF could be due to the induction of sodium channel synthesis.
Amygdaloid and basal forebrain direct connections with the nucleus of the solitary tract and the dorsal motor nucleus
Authors: Schwaber JS , Kapp BS , Higgins GA , Rapp PR
Published: March 2018

Although the amygdala complex has long been known to exert a profound influence on cardiovascular activity, the neuronal and connectional substrate mediating these influences remains unclear. This paper describes a direct amygdaloid projection to medullary sensory and motor structures involved in cardiovascular regulation, the nucleus of the solitary tract (NTS) and the dorsal motor nucleus (DVN), by the use of autoradiographic anterograde transport and retrograde horseradish peroxidase (HRP) techniques in rabbits. Since all of these structures are highly heterogeneous structurally and functionally, details of the specific areas of the neuronal origin and efferent distribution of the projection were examined in relation to these features and with reference to a cytoarchitecture description of the relevant forebrain regions in the rabbit. Amygdaloid projections to the NTS and DVN, as determined from HRP experiments, arise from an extensive population of neurons concentrated exclusively within the ipsilateral central nucleus and confined to and distributed throughout a large medial subdivision of this nucleus. Projection neurons, however, also distribute without apparent interruption beyond the amygdala dorsomedially into the sublenticular substantia innominata and the lateral part of the bed nucleus of the stria terminalis and thus delineate a single entity of possible anatomical unity across all three structures, extending rostrocaudally within the basal forebrain as a diagonal band. Descending central nucleus connections, based upon autoradiographic experiments, project heavily and extensively to both the NTS and the DVN. Within both nuclei, the projections have a highly specific distribution pattern, appearing to correspond largely to structural subdivisions, including the dorsomedial, medial, ventrolateral, ventral, and commissural NTS, and to cell group “a,” a caudally located dorsomedial region, and peripheral regions of the DVN, some of which appear to be involved in cardiovascular regulation. The existence of such an extensive projection system connecting these specific regions is significant evidence in support to its potential for participation in the amygdaloid expression of cardiovascular influences and has important implications for the cellular analysis of the functional role of these influences.