bluuebunny/crossref_metadata_2025 huggingface dataset:
Nonrepinephrine-containing locus coeruleus neurons in behaving rats exhibit pronounced responses to non-noxious environmental stimuli
Authors: Aston-Jones G , Bloom FE
Published: March 2018

The effect of sensory stimulation on discharge in norepinephrine- containing locus coeruleus (NE-LC) neurons was studied in unanesthetized behaving rats. Single unit and multiple unit extracellular recordings demonstrated consistent patterns of response. (1) Short latency (15-to 50-msec), transient, biphasic changes in discharge were elicited predictably by non-noxious auditory, visual, and somatosensory stimuli; individual recordings typically exhibited polysensory responsiveness. (2) Sensory-evoked field potentials (FPs) were synchronized with unit responses simultaneously recorded from the same electrodes. (3) The magnitudes of sensory-evoked response varied as a function of vigilance, so that the largest responses occurred for stimuli which awakened animals and the least responsiveness was exhibited during uninterrupted sleep. (4) Sensory responsiveness decreased during grooming and sweet water consumption, similar to the results for sleep. (5) Characteristic response properties were topographically homogeneous throughout the NE-LC. (6) Discharge was synchronized markedly among neurons in multiple unit populations during phasic robust responses. These results are interpreted in light of the preceding report (Aston-Jones, G., and F.E. Bloom (1981) J. Neurosci. 1: 876–886) and studies of the postsynaptic effects of NE to indicate that the NE-LC system may function more in phasic processes than in modulation of the tonic arousal level. We propose that pronouced NE-LC discharge may enhance activity within target cell systems primarily concerned with processing salient external stimuli and suppress cental nervous system activity related more to tonic, vegetative functions. Thus, the NE-LC system may bias global behavioral orientation between stimuli in the external versus internal environments.
Cellular interactions and pattern formation in the development of the visual system of Daphnia magna (Crustacea, Branchiopoda). II. Induced retardation of optic axon ingrowth results in a delay in laminar neuron differentiation
Authors: Macagno ER
Published: March 2018

Groups of embryonic photoreceptors in one side of the compound eye of Daphnia were irradiated with an ultraviolet microbeam at a stage when the cells were postmitotic but had yet to elaborate axons. Immediately after irradiation, the embryos were placed under fluorescent illumination. On the average, 16 of the irradiated photoreceptors were killed by the exposure. Previous observations suggest that an approximately equal number were rescued by the post-irradiation fluorescent illumination. The schedule of differentiation of the rescued photoreceptors was affected such that their axons arrived at the target region in the optic lamina from 2 to 10 hr after they would have normally. Serial section electron microscopic analysis showed that differentiation of laminar neurons contacted by the delayed axons also was delayed by a length of time corresponding to the delay in axon arrival. These and previous observations indicate that the differentiation of laminar neurons is triggered by contact with optic axons and can be initiated over a period of several hours after these cells become postmitotic.
Picrotoxinin and diazepam bind to two distinct proteins: further evidence that pentobarbital may act at the picrotoxinin site
Authors: Davis WC , Ticku MK
Published: March 2018

alpha-[3H]Dihydropicrotoxinin (DHP) and [3H]diazepam binding proteins were solubilized from rat brain membranes with 1% Lubrol-Px. Gel filtration of the Lubrol-solubilized fraction revealed that [3H]DHP and [3H]diazepam bind to two distinct peaks with apparent molecular weights of 185,000 and 61,000, respectively. The signal-to-noise ratio of [3H]DHP binding to 185,000-dalton fractions was improved significantly. [3H]DHP bound to the 185,000-dalton fraction with two binding constants. Muscimol and pentobarbital, while enhancing [3H]diazepam binding to membrane and crude Lubrol-solubilized fractions, failed to enhance [3H]diazepam binding to the 61,000-dalton fraction. Pentobarbital inhibited the binding of [3H]DHP to the 185,000-dalton fraction with an IC50 value of 60 +/- 12 micro M. The binding of [3H]DHP alos was inhibited by several depressant and convulsant drugs which affect gamma-aminobutyric acid (GABA)-mediated transmission. These results provide strong evidence that picrotoxinin and diazepam bind to two distinct proteins and that pentobarbital may act at the picrotoxinin-sensitive site of the benzodiazepine . GABA receptor . ionophore complex.
The laminar origin and distribution of the crossed tectoreticular pathways
Authors: Holcombe V , Hall WC
Published: March 2018

The superior colliculus is the source of a prominent descending pathway which crosses the midline in the mesencephalon and projects to the paramedian pontine reticular formation. The primary goal of the present study was to identify the cells in the superior colliculus of the grey squirrel which give rise to this pathway by using a combination of anterograde and retrograde tracing techniques. Results from the anterograde studies demonstrated the course and terminal distribution of this pathway and suggested that its laminar origin is the intermediate grey layer, stratum griseum intermediale. The retrograde studies were used to confirm the results of the anterograde experiments and to provide a more quantitative estimate of the laminar distribution of the cells which give rise to this pathway. In most cases, over 90% of the cells retrogradely labeled following injections of horseradish peroxidase along the course of this pathway were located in the intermediate grey lamina. This origin is in contrast to that of the ipsilateral tectoreticular pathway which originates primarily in stratum griseum profundum (Holcombe, V., and W. C. Hall (1981) Neuroscience 6: 255–260) and suggests that these two grey layers of the deep tectum are functionally distinct.
Morphology and synaptic connections of ultrafine primary axons in lamina I of the spinal dorsal horn: candidates for the terminal axonal arbors of primary neurons with unmyelinated (C) axons
Authors: Gobel S , Falls WM , Humphrey E
Published: March 2018

Neurons in Rexed's lamina I have the bulk of their dendritic arbors confined within this lamina. This study examines the morphology and synaptic connections of primary axons which generate axonal endings in lamina I of the spinal dorsal horn and are in position to deliver their inputs directly to lamina I neurons. Primary axons were made visible for light and electron microscopical study by applying horseradish peroxidase (HRP) to the severed central stumps of cervical and lumbar dorsal roots and allowing sufficient time for the orthograde movement of the HRP into the terminal axonal arbors. Golgi preparations provided supplementary light microscopical views of these axons. Lamina I receives the terminal arborization of two very different kinds of primary axons. One of these generates many ultrafine endings along unbranched, long rostrocaudally oriented, strand-like collaterals which arise from thin parent branches in Lissauer's tract. In view of these thin parent branches, most ultrafine primary axons are considered to be unmyelinated (C) primary axons. The second kind of primary axon generates large caliber endings on branched collaterals. These arise from relatively thick parent branches in Lissauer's tract which, on the basis of their size, are considered to be myelinated (A delta) primary axons. The scalloped endings of both primary axons lie in the interior of glomeruli where they form axodendritic synapses on small dendritic shafts and spines. It is at these synapses that these two kinds of primary axons are thought to transfer nociceptive and thermal inputs directly to the dendritic arbors of lamina I neurons. Transmitter release at these axodendritic synapses in response to primary inputs can be modified, probably diminished or inhibited, by synaptic events within the glomeruli from at least three sources. Synaptic vesicle- containing dendrites form dendroaxonic synapses on primary endings and two kinds of axons form axoaxonic synapses either on primary endings or on the intervaricose segments of the primary axons.
Membrane potential of olfactory bulb synaptosomal fractions: characterization with the lipophilic cation tetraphenylphosphonium
Authors: Rochel S , Lichtstein D , Blume AJ , Margolis FL
Published: March 2018

The membrane potential of olfactory bulb synaptosomal fractions was monitored with the lipophilic cation tetraphenylphosphonium (TPP+), which has been reported to distribute across membranes according to the Nernst equation. The properties of the synaptosomal membrane potential as monitored with TPP+ were similar to those reported for neural tissues using other measurement techniques. There is an electrical potential (delta psi) of -64 and -77 mV in the P1 and P2 synaptosomal fractions, respectively. This potential is due primarily to the K+ diffusion gradient across the synaptosomal membrane. The influence of ouabain on TPP+ accumulation indicates that the (Na+,K+)-ATPase electrogenicity contributes about -20 mV to the resting synaptosomal membrane potential. Veratridine induced a decline in TPP+ accumulation which was blocked by tetrodotoxin or by the omission of Na+ from the medium. A significant mitochondrial contribution to TPP+ accumulation, which varied as a complex function of TPP+ concentration in the medium in a manner indicating that TPP+ interfered with the maintenance of mitochondrial potential, was observed. This mitochondrial contribution could be eliminated by performing the experiments anaerobically in the presence of oligomycin. The results are discussed with relation to the future possible use of TPP+ for delta psi measurements in synaptosomal preparations.
Use of an experimental autoimmune model to define nerve growth factor dependency of peripheral and central substance P-containing neurons in the rat
Authors: Ross M , Lofstrandh S , Gorin PD , Johnson EM , Schwartz JP
Published: March 2018

Rats exposed to maternal antibodies against nerve growth factor (NGF) in utero and in milk have been used to investigate the developmental dependency of various substance P-containing neurons on NGF. Substance P and other peptides were measured by radioimmunoassays. The substance P content of sensory ganglia, spinal cord, and skin was depleted 40 to 60% in anti-NGF-treated rats. These results demonstrate the NGF dependence of substance P-containing neurons in sensory ganglia. Opiate binding in the spinal cord was not changed despite the large depletion in substance P: the Bmax and KD were the same in control and treated animals. The results suggest that opiate receptors may not be located presynaptically on substance P-containing primary afferents. Among the peripheral tissues which were assayed (ileum, submaxillary gland, retina, and adrenal), substance P decreased only in the adrenal, suggesting innervation by a NGF-dependent substance P-containing neuron. No changes were detected in the substance P content of nine different brain regions, in agreement with previous observations on the lack of effect of NGF on central neurons.
Density, soma size, and regional distribution of rabbit retinal ganglion cells
Authors: Oyster CW , Takahashi ES , Hurst DC
Published: March 2018

Cell soma area or diameter distributions are generally very skewed and present some unusual problems in characterization and description. In this study of ganglion cell soma size in rabbit retina, our conclusions are based on a statistical method which not only characterizes this particular neuronal population but which also may be of considerable value in other species and other parts of the nervous system. To facilitate comparisons between retinas, we used ganglion cell density as the measure of retinal location. The rabbit retina has a horizontally extended area centralis, the visual streak, which we show to have a uniformly high peak cell density along most of its length. Cell density maps were used to estimate the total number of ganglion cells in the retina; the mean for three retinas was about 406,000 cells, which corresponds well to an earlier count of optic nerve axons (394,000 +/- 20,000; Vaney, D.I., and A. Hughes (1976) J. Comp. Neurol. 170: 241–252). Contrary to other reports, we could not find any large differences in ganglion cell size distributions between the inferior peripheral retina and the visual streak nor could we confirm the report of a large cell area temporalis (Provis, J. M. (1979) J. Comp. Neurol. 185: 121–138). Cell size distributions in the superior and inferior retina were very different, however, and, within the inferior retina, there was a small but systematic change in cell size between the periphery and the visual streak. In general, small and medium size cells were present in nearly constant proportions throughout the inferior retina, while the large ganglion cells showed a small decrease in proportion from the periphery to the visual streak; the decline in large cells was a linear function of cell density. In terms of ganglion cell soma size, there was no sharp distinction between the visual streak and the peripheral retina.
Specificity and plasticity of retinotectal connections: a computational model
Authors: Whitelaw VA , Cowan JD
Published: March 2018

A computational model is presented which simulates the development and regeneration of orderly connections between retinal fibers and tectal cells in frogs and goldfish. The model distinguishes two aspects of retinotectal connectivity: (1) the contact adhesion between retinal fibers and tectal cells as mediated by fixed chemospecific markers and (2) the formation of modifiable synapses between them. Chemospecificity is assumed to be an intrinsic property of both the retina and tectum and is modeled as a graded distribution of a binding determinant or marker. Synapse formation depends upon the timing of neural activity as well as on the intinsic chemospecificity of retinotectal contacts. In addition to the normal development and regeneration of the retinotectal map, the model simulates the compressed, expanded, translocated, and rotated maps that have been found in surgically manipulated contexts. There examples of plasticity in the retinotectal map can be simulated without assuming any changes in the marker distributions. Moreover, the model demonstrates that a very shallow gradient of a single marker suffices to organize retinotectal connections in a variety of contexts.
gamma-Aminobutyric acid concentration, L-glutamate 1-decarboxylase activity, and properties of the gamma-aminobutyric and postsynaptic receptor in cobalt epilepsy in the rat
Authors: Ross SM , Craig CR
Published: March 2018

Crude mitochondrial synaptosomal (P2) fractions were used to measure L- glutamate 1-decarboxylase (GAD) activity, and crude synaptic membranes were isolated from rat brains and used to determine gamma-aminobutyric acid (GABA) concentration and postsynaptic GABA receptor binding characteristics in rats with cobalt, copper, or glass implanted in right and left cerebral cortices. Copper was employed as a positive metal control because it elicits a morphological profile similar to that of cobalt but is non-epileptogenic. From tissue adjacent to the lesion, GAD activity was assessed by counting trapped 14CO2 liberated from [14C]glutamate and was reduced maximally to 25% of glass controls 7 days following cobalt insult, a period of peak seizure incidence. No reduction in GAD activity was observed 1 or 21 days after cobalt treatment or at any time period in copper-or glass-treated animals. A radioligand [3H]GABA receptor assay was utilized to determine GABA levels, postsynaptic receptor number (Bmax), and the affinity of the postsynaptic receptor for the ligand (KD) in tissue surrounding the lesion. GABA concentration was reduced maximally to 47% of glass controls 7 days following cobalt implantation. Scatchard plot analysis of tissue adjacent to the cobalt lesion revealed a significant increase in apparent receptor density (Bmax) to 200% of glass controls 7 days after bilateraL cobalt implantation (Bmax = 3.97 +/- 0.83 pmol/mg of protein, cobalt versus 1.36 +/- 0.17, glass control). Moreover, at 7 days, no change in kinetic parameters was noted after copper treatment. From days 7 to 21, the density (Bmax) of postsynaptic GABA receptors in cobalt-treated tissue appears to return slowly to glass control values. Results from the present study suggest that degeneration of the GABA pathway in the frontal cortex of the cobalt-epileptic rat occurs and, coupled with the increased Bmax, may represent a “denervation supersensitivity” phenomenon.
Mechanisms of septal lamination in the developing hippocampus analyzed by outgrowth of fibers from septal implants. II. Absence of guidance by degenerative debris
Authors: Lewis ER , Cotman CW
Published: March 2018

In previous study (Lewis, E.R., and C. W. Cotman (1980) Brain Res. 96: 307--330; E. R. Lewis and C. W. Cotman, submitted for publication), we have shown that septal tissues grafted to the brain of a neonatal rat will extend fibers into special terminal laminae within the hippocampal formation of the recipient. As a consequence of the implantation surgery, neurons in the developing entorhinal cortex are ablated and it is possible that processes of implanted cells may be guided by degenerating afferent fibers in the host. In order to test this hypothesis, we have characterized the distribution of degeneration argyrophilia that results from the implant surgery and the time course of its removal and examined the growth of septal implants in a host brain devoid of observable degenerative debris. The pattern of degeneration argyrophilia shortly after the implantation surgery did not correspond to the pattern of implant-associated AChE staining in the host hippocampal formation. By 72 hr after surgery, the great majority of argyrophilic debris had been removed. Implants placed in a cavity created 72 hr after surgery demonstrated excellent viability and produced the typical pattern of AChE staining in the hippocampal formation of the host. This suggests that the presence of degenerating host axons is not necessary to guide the ingrowth of axons and establish septohippocampal laminated fields.
Dopamine and [D-ALA2, D-Leu5]enkephalin inhibit the electrically stimulated neurohypophyseal release of vasopressin in vitro: evidence for calcium-dependent opiate action
Authors: Lightman SL , Iversen LL , Forsling ML
Published: March 2018

The effects of both dopamine and enkephalin agonists were assessed on electrically stimulated vasopressin secretion from the isolated neural lobe. Both dopamine (10(-6) M) and the dopamine agonist ADTN (2-amino- 6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene; 10(-6) M) significantly reduced the stimulated release of vasopressin. This reduction in vasopressin secretion was prevented by the dopamine antagonist sulpiride (10(-6) M). [D-Ala2, D-Leu5]Enkephalin (DADLE) also inhibited vasopressin release and its effect was additive to that of ADTN. The effect of DADLE was prevented by the opiate antagonist naloxone and was also sensitive to the calcium content of the medium. Low calcium concentrations markedly increased the inhibitory effect of DADLE, while high concentrations abolished its effect. These findings provide evidence of a direct inhibitory action of both dopamine and enkephalins at the level of the neural lobe and suggest that the effect of enkephalins may be intimately related to calcium-sensitive neurosecretory events.
The specificity of extracellular glycoprotein complexes in mediating cellular adhesion
Authors: Schubert D , LaCorbiere M
Published: March 2018

Complexes containing glycoproteins and glycosaminoglycans were released into the culture medium by both smooth and skeletal muscle cells. The particles, termed adherons, from three smooth muscle cell lines promoted cell-substratum adhesion of a clonal sympathetic nerve cell line, PC12. In contrast, the glycoprotein complexes from three skeletal muscle preparations inhibited the adhesion of PC12 cells to Petri dish surfaces. The skeletal muscle adherons all sedimented in calcium-free sucrose gradients with an S value of 16, while the smooth muscle particles had a sedimentation value of 12. Although both classes of adherons contained fibronectin and collagen, hyaluronic acid was present only in those from skeletal muscle. An antiserum prepared against skeletal muscle adherons blocked myoblast adhesion to skeletal muscle adherons but did not alter PC12 adhesion to smooth muscle adherons. These data suggest that the glycoprotein complexes released by muscle have some intrinsic specificity with respect to their ability to mediate cellular adhesion.
Carnosine in primary afferents of the olfactory system: an autoradiographic and biochemical study
Authors: Burd GD , Davis BJ , Macrides F , Grillo M , Margolis FL
Published: March 2018

Previous in vivo studies have shown that beta-alanine is incorporated specifically into the dipeptide L-carnosine (beta-alanyl-L-histidine). In the present study, we administered beta-[3H]alanine to the nasal cavity of hamsters and used biochemical analyses to identify the radioactively labeled compounds in the olfactory epithelium and olfactory bulb and autoradiography to demonstrate the localization and transport of the label in the primary afferents of the olfactory system. The olfactory epithelium and lamina propria were labeled intensely 6 hr after intranasal beta-[3H]alanine administration. At this survival time, 61% of the radioactivity in the olfactory epithelium was present in the carnosine fraction, while 37% of the label remained in the beta-alanine fraction. After 24-hr and 4-day survival periods, greater than 82% of the radioactivity was present in the carnosine fraction, and the olfactory receptors and bundles of axons were labeled preferentially. The olfactory nerve and glomerular layers of the main olfactory bulb were labeled intensely at 6 and 24 hr after beta-[3H]alanine administration; much less label was present in these layers at 4 days survival. At all three of these survival times, greater than 84% of the radioactivity in the olfactory bulb was present in the carnosine fraction. No label was present in the olfactory epithelium or bulb 18 days after beta-[3H]alanine administration. While the autoradiographic labeling over the structures of the accessory olfactory system was consistently less intense than that over the main olfactory system structures, the patterns of labeling were similar over the four survival times. Intranasal alpha-[3H]alanine administration resulted in some labeling in the primary afferent fibers, but the labeling did not have the specificity nor the same time course over the four survival times that was observed after beta-[3H]alanine administration. The results are consistent with the hypothesis that carnosine is a neurotransmitter or neuromodulator in the olfactory neurons. The results also suggest that carnosine may play a similar role in the vomeronasal neurons.
Effects of monocular deprivation on the structure-function relationship of individual neurons in the cat's lateral geniculate nucleus
Authors: Friedlander MJ , Stanford LR , Sherman SM
Published: March 2018

The retino-geniculo-cortical pathways of the cat composed of at least three parallel channels. The neurons in these channels (W-, X-, and Y- cells) have different physiological properties. In earlier studies, we used a direct structure-function for analysis for individual geniculate neurons in normal cats. This was accomplished by electrophysiological characterization of the neuron followed by intracellular iontophoresis of horseradish peroxidase into the same neuron. By this technique, we demonstrated that W-, X-, and Y-cells have distinctive morphological features in the lateral geniculate nucleus of the act. We have extended this analysis in cats reared with monocular eyelid suture to 24 geniculate neurons innervated by the sutured eye in lamina A or A1. Ten of the 24 neurons (42%) had abnormal structure-function relationships. All but 1 of the normal cells were X-cells. Abnormalities included: (1) Y-cells with normal physiology but abnormally small somata; (2) Y-cells with abnormal physiology and morphology, including poor responsiveness and unusually thin, tortuous, and beaded dendrites; (3) visually unresponsive cells with morphology similar to that of the physiologically abnormal Y-cells; and (4) cells with the physiology of normal X-cells but the morphology of normal Y-cells. Furthermore, soma size measurements indicate that the abnormally small somata found in deprived geniculate laminae result from a selective effect on Y-cells.
4 S RNA in regenerating optic axons of goldfish
Authors: Ingoglia NA
Published: March 2018

Previous experiments have demonstrated that 4 S RNA is transported axonally during the reconnection period of optic nerve regeneration in goldfish. The present experiments were performed to determine whether 4 S RNA is transported axonally during later, maturational stages of nerve regeneration and to examine some of the characteristics of 4 S RNA in regenerating axons. [3H]Uridine was injected into both eyes of fish 18 days (near the time of reconnection) after bilateral optic nerve crush and the fish were sacrificed at various times up to 180 days after injection. [2H]RNA was isolated by phenol extraction and ethanol precipitation from 24 pooled tecta and fractionated by SDS- polyacrylamide tube gel electrophoresis. Data from these experiments showed that 70% of the [3H]RNA is present as 4 S RNA 12 days after injection, and 60 days after injection, this value is still approximately 50%. When nerves were cut 36 days after injection (54 days post-crush) and allowed to degenerate for 6 days before determining tectal [3H]RNA, the majority of the 4 S[3H]RNA was lost from the tectum. This indicates that up to 36 days after injection, 4 S [3H]RNA remains within regenerating axons and that it is unlikely that significant amounts of axonally transported 4 S RNA are transferred out of the axon to surrounding cells. In other experiments, the time of sacrifice after injection was held constant and the time of injection after nerve crush was varied. Analysis of tectal [3H]RNA showed that the major period of axonal transport of 4 S [3H]RNA was in early stages of regeneration at 24 and 36 days after nerve crush and that the amount of 4 S [3H]RNA which is transported axonally decreased at later time points. Calculations of the amount of axonal 4 S [3H]RNA versus what is synthesized in periaxonal cells gave results suggesting that 4 S RNA in regeneration axons turns over relatively slowly when compared with 4 S RNA in tectal cells.
The transplantation of eyes to genetically eyeless salamanders: visual projections and somatosensory interactions
Authors: Harris WA
Published: March 2018

Eyes were transplanted from normal axolotls to eyeless mutants, and several anatomical and physiological observations were made on the central visual centers in these animals. Some central projections were bilateral to the optic centers of the thalamus and midbrain, some traveled ipsilaterally to the same centers, and the rest grew down the spinal cord. This is similar to what has been found in eyes transplanted to normal hosts. The type of projection made in eyeless hosts correlated with the site of nerve entry into the CNS as in control hosts. Thus, the transplanted projection did not appear to be influenced by the host's optic nerves and tracts or lack of them. In spite of the transplanted optic fibers' taking abnormal paths, they made normally organized topographic maps on the host tecta. The visual and somatosensory topographic projections to the tectum were found to be in near perfect register normally, but in eyeless mutants to which rotated eyes had been transplanted, they were not. Acetylcholinesterase activity, found in the primary optic neuropil in normal animals, was greatly diminished in eyeless mutants, yet normal mutants with grafted eyes. Finally, transplantation of an eye to an eyeless mutant corrected the abnormally dark pigmentation caused by eyelessness but only in those cases of bilateral central innervation.
Specific uptake of norepinephrine and dopamine by homogenates of rat cerebral cortex after locus ceruleus lesion
Authors: Logan WJ , Harik SI
Published: March 2018

Unilateral injection of 6-hydroxydopamine into the locus ceruleus led to long lasting depletion of norepinephrine in the ipsilateral parietal cerebral cortex of the rat up to 8 weeks after injection. The uptake of both norepinephrine and dopamine by homogenates of parietal cortex was decreased markedly on the ipsilateral, but not on the contralateral, side. The uptake of four other neurotransmitter candidates or precursors was unaffected by the lesion. Desipramine (DMI) markedly inhibited the uptake of both norepinephrine and dopamine by cortical preparations from the contralateral side and from control rats, but this effect was not seen in preparations from the norepinephrine- depleted, ipsilateral cortex. The decreases DMI-sensitive uptake of norepinephrine or dopamine was highly correlated with decreased norepinephrine in the ipsilateral cortex. These results suggest that the specific uptake of norepinephrine and dopamine is a valid marker of noradrenergic innervation of the parietal cortex and that dopamine seems to be accumulated primarily by norepinephrine terminals in this region. Two and 8 weeks after locus ceruleus lesion, a DMI-insensitive, benztropine-sensitive dopamine uptake becomes apparent in ipsilateral cortical preparations, This may represent proliferation or increased function of dopaminergic cortical projections, compensating for noradrenergic denervation.
Cell size changes in the lateral geniculate nuclei of normal and monocularly deprived cats treated with 6-hydroxydopamine and/or norepinephrine
Authors: Hitchcock PF , Hickey TL
Published: March 2018

Given the proposed role of catecholamines in controlling cortical plasticity in the cat (Kasamatsu, T., J. D. Pettigrew, and M. Ary (1979) J. Comp. Neurol. 185: 163–182), we were interested in whether evidence of such control also could be found in the dorsal lateral geniculate nucleus. We undertook geniculate cell size measurements in 26 normal or monocularly deprived cats, 23 of which had been used in cortical recording studies concerned with catecholamine-induced plasticity. For animals grouped according to experimental treatments, the results can be summarized as follows: (1) in visually normal animals, neither intraventricular injections of 6-hydroxydopamine (6- OHDA) nor local perfusions of norepinephrine (NE) cause changes in geniculate cell size. (2) In otherwise untreated kittens, 1 week of monocular deprivation begun in the 6th week of life results in quite obvious changes in geniculate cell size. (3) Intraventricular injections of 6-OHDA do not appear to prevent deprivation-induced changes in geniculate cell size. (4) Older NE-treated kittens and adult cats that are monocularly deprived for a brief period either late in the critical period or after the critical period has ended do not show deprivation-induced changes in geniculate cell size in either hemisphere. (5) In younger kittens which had been first injected with 6- OHDA intraventricularly and then monocularly deprived for a brief period early in the critical period, there is no evidence to suggest that a local perfusion of NE enhances deprivation-induced changes in geniculate cell size.
Internalization of nerve growth factor by pheochromocytoma PC12 cells: absence of transfer to the nucleus
Authors: Rohrer H , Schafer T , Korsching S , Thoenen H
Published: March 2018

he intracellular distribution of 125I-labeled nerve growth factor (NGF) in rat pheochromocytoma PC12 cells was studied by quantitative electron microscopic (EM) autoradiography and by subcellular fractionation. PC12 cells were grown as monolayer cultures in medium supplemented with serum in the presence of 125I-NGF. EM autoradiography showed that 125I-NGF was localized at the plasma membrane and cytoplasmic compartments but did not accumulate in the nuclear chromatin or in the nuclear membrane compartment of cells analyzed after 1 hr and 1, 2, and 8 d of incubation with 125I-NGF. 125I-NGF also was not detected in nuclear subcellular fractions prepared from cells grown in serum-supplemented medium either in suspension for 1 d or in monolayer cultures for 1 to 8 d. In contrast, and in confirmation of the results of Yankner and Shooter (Yankner, B. A., and E. M. Shooter (1979) Pro. Natl. Acad. Sci. U. S. A. 76: 1269–1273), about 60% of the cell-bound 125I-NGF was found in the nuclear pellet after cell fractionation if the cells had been kept previously in suspension for 1 d in phosphate-buffered saline supplemented with 0.2% glucose, 0.1% bovine serum albumin, and 125I-NGF. The ultrastructure of PC12 cells grown under such conditions, however, revealed signs of varying degrees of damage. Autoradiography of the nuclear pellet from these cells showed the grains to be located mainly over damaged nuclei or over cell debris between nuclei. It is concluded that NGF, after binding to specific receptors at the plasma membrane, is transferred to membrane- confined cytoplasmic compartments but does not have to be transferred further to the nuclear membrane or to the nuclear chromatin as a prerequisite for its physiological action.
Isolation, morphology, and protein and glycoprotein composition of synaptic junctional fractions from the brain of lower vertebrates: antigen PSD-95 as a junctional marker
Authors: Nieto-Sampedro M , Bussineau CM , Cotman CW
Published: March 2018

Synaptic junction (SJ) fractions were isolated from the brains of the gray shark, bonito, common frog, several reptiles, and common chicken and compared to those prepared from mammalian brain. All SJ preparations, as judged by electron microscopic analysis, were at least 85% pure, consisting primarily of postsynaptic densities (PSDs) with or without an overlying plasma membrane and, to a lesser extent, of complete synaptic junctions. Complete junctions were less abundant in preparations from lower vertebrates. The electrophoretic pattern of SJs from different vertebrate species showed considerable conservation of the major protein bands. The most abundant were fibrous proteins, especially tubulins, actin, and the PSD-specific polypeptide with a molecular weight of 52,000 (PSD-52). Glycoproteins capable of binding concanavalin A were present in SJs from all vertebrates; their apparent molecular weight and relative abundance were characteristic of each animal order examined, showing more similarities in species more closely related phylogenetically. Finally, a protein (antigen PSD-95) previously shown to be located specifically in the postsynaptic densities of the mammalian brain was present in all species. The binding of antibody specific to this protein decreased with descending phylogenetic order from mammals to shark. Nonetheless, PSD-95 was present in all vertebrate species and appeared to be a general specific marker for PSDs.
Ontogenetic changes in the projections of neocortical neurons
Authors: Ivy GO , Killackey HP
Published: March 2018

Development changes in the origins of contra- and ipsilateral projections from the rat parietal cortex were examined using the retrograde transport of horseradish peroxidase and of the fluorescent dyes fast blue and nuclear yellow. The aim of the study was to determine the fate of the neurons which send axons through the corpus callosum in the neonatal, but not the young adult, rat. 1. Neurons which project across the corpus callosum at postnatal day 8 (PND 8), but not at PND 20 or later, do not die; they merely lose their contralateral processes. 2. At PND 8, many of these neurons--in particular, those in lamina Va of the barrel field area--project simultaneously across the corpus callosum and to the ipsilateral motor cortex. 3. By PND 20 and later, many neurons in lamina Va of the barrel field area still project to the ipsilateral motor cortex but not across the corpus callosum. We conclude that at least some neocortical neurons initially elaborate more axonal processes than they will maintain and that they selectively eliminate major projections during development.
Effects of hypophysectomy and dexamethasone administration on central and peripheral S-adenosylmethionine levels
Authors: Wong DL , Zager EL , Ciaranello RD
Published: March 2018

The effects of hypophysectomy and dexamethasone administration on S- adenosylmethionine (SAM) levels in the adrenal, liver, pineal, and various brain regions were examined to determine the central and peripheral relationships between SAM and glucocorticoids in vivo. A simple and sensitive radioenzymatic assay was developed to measure tissue SAM concentrations following removal of its demethylated metabolite, S-adenosylhomocysteine (SAH), whose presence precludes accurate SAM determinations. Three patterns of SAM control emerged. In the adrenal, pineal, striatum, and midbrain, SAM levels fell after hypophysectomy and were restored by dexamethasone administration. In the thalamus, hypothalamus, hippocampus, and cerebellum, SAM levels increased after hypophysectomy and were not altered further by dexamethasone administration. In the liver, cortex, septum, and pons- medulla, SAM levels were not affected by either hypophysectomy or dexamethasone administration. These results suggest that multiple controls regulate SAM levels in vivo. The control factors are both highly tissue and region specific. While glucocorticoids are an important regulatory factor of SAM in some peripheral and CNS tissues, they are not the sole regulatory factor. In CNS regions where hypophysectomy increases SAM levels but glucocorticoid administration does not reverse the effects, other hypothalamic hormones, pituitary hormones, or neural factors may be involved in SAM regulation. Likewise, in regions where neither hypophysectomy nor glucocorticoid administration affects SAM levels, hypothalamic or neural factors may be involved even though pituitary factors do not appear to be important.
Analysis of microtubule number and length in cytoskeletons of cultured chick sensory neurons
Authors: Letourneau PC
Published: March 2018

In order to examine the continuity of individual microtubules in growing neurites, microtubules were observed and counted in whole mounted cytoskeletons of chick embryo sensory neurons. At neurite branch points, the microtubules of the proximal segment are divided between the distal segments without the addition of microtubules to the distal branches. Few microtubules ends were seen in the cytoskeletons, and on occasion, the same number of microtubules was counted at widely separated points along a neurite segment. I conclude that microtubules are long in embryonal neurites, and some may extend the entire length from perikaryon to neurite tip. This may limit where microtubule growth occurs to the perikaryon and the neurite tip, where many microtubule ends are. In addition, the great length of most neuritic microtubules may explain why collateral sprouting is rare along embryonal neurites.
Role of the suprachiasmatic nuclei in the circadian system of the house sparrow, Passer domesticus
Authors: Takahashi JS , Menaker M
Published: March 2018

The suprachiasmatic nuclei (SCN) of the hypothalamus are necessary for the persistence of free running circadian activity rhythms in house sparrows. Suprachiasmatic lesions abolish circadian locomotor rhythms in constant darkness. The locomotor activity of lesioned sparrows was analyzed with two different power spectral analysis methods and was found to be arrhythmic. There was a weak correlation between the extent of damage to the SCN and the relative amplitude of the power spectral density in the circadian frequency range. In light-dark cycles (LD 12:12), the locomotor behavior of lesioned sparrows was rhythmic and similar to that of intact birds. However, entrainment was disrupted in SCN-lesioned sparrows exposed to a short photoperiod light cycle (LD 1:24). These results demonstrate that the SCN are crucial for the generation of overt circadian rhythmicity in birds. The fact that SCN lesions abolish circadian rhythms in sparrows and several mammalian species suggests that vertebrate circadian organization may be based on differentially weighted interactions among the pineal, the SCN, and perhaps other brain regions.
Striatal binding of 2-amino-6,7-[3H]dihydroxy-1,2,3,4- tetrahydronaphthalene to two dopaminergic sites distinguished by their low and high affinity for neuroleptics
Authors: List SJ , Wreggett KA , Seeman P
Published: March 2018

In order to develop more selective methods for labeling brain dopamine receptors, this study describes in detail the properties of 2-amino- 6,7,-[3H]dihydroxy-1,2,3,4,-tetrahydronaphthalene ([3H] ADTN) binding to dopaminergic sites in rat, calf, and human brain. [3H]ADTN labeled two distinct types of dopaminergic binding sites in the brain striatum of the rat, calf, and human. Very low concentrations of dopamine and dopaminergic catecholamines (with IC50 values of 1 to 10 nM) inhibited the binding of [3H]ADTN to both sites. Neuroleptics, however, inhibited the binding of [3H]ADTN in two distinctly separate concentration ranges, with IC50 values of 0.15 to 40 nM at one site and 100 and 50,000 nM at the other site. The site with high affinity for dopamine and low affinity for neuroleptics had binding properties that corresponded to those of the previously characterized D3 site (List, S., M. Titeler, and P. Seeman (1980) Biochem. Pharmacol. 29: 1621– 1622). The [3H]ADTN binding site with high affinity for neuroleptics demonstrated binding characteristics similar to a site labeled by 3H- Neuroleptics (Sokoloff, P., M. P. Martres, and J. C. Schwartz (1980) Naunyn Schmiedebergs Arch. Pharmacol. 315: 89–102). [3H]Apomorphine appeared to label the same two sites as [3H]ADTN, while [3H]dopamine labeled only the D3 site. Scatchard analysis of [3H]ADTN or [3H]apomorphine binding, under conditions for selective labeling of the low affinity neuroleptic site (D3) and the high affinity site for neuroleptics, detected a density of 70 fmol/mg of protein for each. The density of the D3 site in the calf striatum (170 fmol/mg of protein) was much greater than that of the high affinity neuroleptic site (50 fmol/mg). In the rat, the dissociation constant (KD) of [3H]ADTN was 2 nM for both sites. [3H]Apomorphine, however, had a higher affinity for the D3 site (KD=1.6 nM) than for the high affinity neuroleptic site (KD=4.2 nM). The present results may explain previously observed species and laboratory differences between the binding of [3H]ADTN, [3H]apomorphine, and [3H]dopamine.
Myotonia, a new inherited muscle disease in mice
Authors: Heller AH , Eicher EM , Hallett M , Sidman RL
Published: March 2018

Electromyographic (EMG) and histological studies were carried out with the new mouse mutant myotonia (mto, autosomal recessive). Affected animals exhibited behavioral myotonia which was apparent at 2 weeks of age. EMG studies revealed myotonic discharges (prolonged repetitive discharges with recurrent variation in amplitude and frequency) in all skeletal muscles tested. These discharges were not affected by peripheral nerve section or by pancuronium bromide, a neuromuscular synapse inhibitor. Qualitative histological study revealed no evidence of skeletal muscle fiber necrosis, grouped atrophy, or inflammation compared toi sex-, age-, and weight-matched controls. Degeneration of myelinated axons in the ventrolateral funiculus of the spinal cord occurred only in older animals and does not explain the functional abnormality of muscle. Both the clinical and electrophysiological features of classical myotonia can be inherited as a single locus autosomal recessive disease in mice.
Ribbon synapses in the developing intact and cultured organ of Corti in the mouse
Authors: Sobkowicz HM , Rose JE , Scott GE , Slapnick SM
Published: March 2018

Over 100 synaptic ribbons were studied in the intact animal from birth to the 23rd day and over 500 were studied in the isolated organ up to 24 days in culture. Our findings suggest that synaptogenesis in the cochlea of the mouse occurs mainly postnatally and lasts at least 14 days. Afferent synapses of young cochleas are characterized by round ribbons which are attached to the presynaptic membrane by two rodlets, each surrounded by a discrete triangular density. The postsynaptic density is continuous and coextends with the presynaptic complex. The single layer of vesicles surrounding the dense body of the ribbon is disrupted by the presynaptic densities. In an afferent synapse of the adolescent animal, the predominant organelle is a plate ribbon--often laminated--which measures on the average approximately 1000 A wide, 2000 A tall, and 1500 A long (one section = 700 A). The ribbon is attached to a presynaptic density, arcuate in form; a row of synaptic vesicles is aligned along each side of the arcuate density. The presynaptic membrane forms a trough accommodating the ribbon. The postsynaptic density exceeds the territory of the ribbon. Similar development of the synapse also may be observed in culture. Structural variability of ribbons (seen especially in culture), clustering of ribbons, multiribbon synapses, and ribbon families seem to be characteristic of early development. The occurrence of ring-like or fenestrated ribbons in the intact adolescent animal suggests a limited life span of the organelle. A decrease in the ribbon population of the outer hair cells, to about 20% of the total number, occurs postnatally in the intact animal. A similar decrease occurs also in culture. This implies that the ribbon population is not affected by the efferent influx. The mature cochlear ribbon appears comparable to those of the retina and some ampullary organs of electric fishes.
Segmental specialization of a leech swim-initiating interneuron, cell 2051
Authors: Weeks JC
Published: March 2018

The physiological and anatomical properties of an unpaired intersegmental interneuron designated cell 205 are described. Cell 205 is unusual among leech neurons in that it combines a variety of functional properties in a single cell. Constant current depolarization of cell 205 initiates and maintains swimming behavior in semi-intact leeches or the swim motor pattern in brainless, isolated nerve cords. During swim episodes elicited by other stimuli, cell 205 is rhythmically active. Current pulses passed into cell 205 during swimming reset the pattern, indicting that it has access to, or may be a member of, the swim central pattern generator (CPG). Cell 205 is the first interneuron in this system to exhibit both swim-initiating and CPG functions. Individual touch, pressure, and nociceptive primary mechanoreceptor neurons polysynaptically excite cell 205, which, in addition, is coupled electrically to the multimodal S interneuron. These inputs may contribute to the initiation and/or modulation of swimming in response to sensory stimuli. Cell 205 shares some common synaptic inputs and outputs with the only other known swim-initiating interneuron, cell 204, but the two cells differ fundamentally in that cell 204 exerts only a tonic effect on the CPG. No synaptic interactions were found between cells 204 and 205, but their excitatory effects on swimming summate. Unlike other swim neurons which are segmentally repeated, cell 205 generally is present only in segment 9, and numerous lines of evidence suggest that it is, in fact, a segmentally differentiated homolog of cell 204.