bluuebunny/crossref_metadata_2025 huggingface dataset:
Hypobaric-ischemic conditions produce glutamate-like cytopathology in infant rat brain
Authors: Ikonomidou C , Price MT , Mosinger JL , Frierdich G , Labruyere J , Salles KS , Olney JW
Published: March 2018

We present a new animal model of perinatal hypoxic/ischemic brain damage and compare this type of brain damage with the excitotoxic type of damage previously described in the brains of infant rats and monkeys treated systemically with glutamate (Glu). Ten-d-old rats with unilateral occlusion of the common carotid artery were subjected to hypobaric conditions for 75 min and sacrificed 0–4 hr later for light and electron microscopic brain examination. The mortality rate was relatively low (12%), and brain damage was evident ipsilateral to the ligated carotid in 94% of surviving animals 4 hr after termination of the hypobaric event. Regions most frequently affected were the medial habenulum, dentate gyrus, caudate nucleus, frontoparietal neocortices, olfactory tubercle, and several thalamic nuclei. The acute cytopathological changes, primarily edematous degeneration of neuronal dendrites and cell bodies, evolved very rapidly, with some neurons manifesting end-stage necrosis at 0 hr (immediately after hypobaric exposure) and others developing such changes over a 1–4-hr period. We conclude that the neurodegenerative reaction induced in infant rat brain by hypoxia/ischemia is indistinguishable from the excitotoxic type of damage exogenous Glu is known to cause. Moreover, in a companion study (Olney et al., 1989) we show that MK-801, a powerful antagonist of the N-methyl-D-aspartate receptor complex (subtype of Glu receptor), protects against neuronal degeneration in this hypobaric/ischemic model. Our results reinforce other recent evidence suggesting that hypoxic/ischemic brain damage is mediated by endogenous Glu or related excitotoxins.
MK-801 prevents hypobaric-ischemic neuronal degeneration in infant rat brain
Authors: Olney JW , Ikonomidou C , Mosinger JL , Frierdich G
Published: March 2018

Recent evidence implicates the endogenous excitatory amino acids, glutamate (Glu) and aspartate, in hypoxic/ischemic neuronal degeneration. In a preceding article (Ikonomidou et al., 1989) we described a new model for studying hypoxic/ischemic neuronal degeneration in the infant rat brain that entails unilateral common carotid artery ligation followed by exposure to a partial vacuum for 75 min. Promising features of this model include a low mortality rate and high incidence of acute brain damage disseminated over numerous brain regions. In addition, there is a striking similarity between the type of cytopathology characterizing this model of hypoxic/ischemic neuronal degeneration and that which has been described in infant animals treated with Glu. MK-801 is a powerful antagonist of the N-methyl-D- aspartate (NMDA) receptor ionophore complex (a subtype of Glu receptor). In the present study, after unilateral carotid artery ligation was performed on 10-d-old rat pups, they were treated either with MK-801 (1 mg/kg i.p.) or saline 15 min before exposure to the hypobaric condition. MK-801 exerted a strong neuroprotective effect without serious side effects; the majority of saline control animals sustained severe brain damage, whereas the majority of MK-801-treated pups had no brain damage. These and other recent findings suggest that the NMDA receptor may play an important role in hypoxic/ischemic neuronal degeneration in the immature brain and provide hope that NMDA antagonists such as MK-801 may be effective in preventing such degeneration.
Time course of structural changes at identified sensory neuron synapses during long-term sensitization in Aplysia
Authors: Bailey CH , Chen M
Published: March 2018

We have used the gill- and siphon-withdrawal reflex of Aplysia californica to explore the morphological basis of the synaptic plasticity that underlies long-term sensitization. In earlier studies (Bailey and Chen, 1983, 1988a), we described 2 classes of structural changes at identified sensory neuron synapses that occur following long- term sensitization: (1) increases in the number, size, and vesicle complement of active zones and (2) an overall increase in the total number of synaptic varicosities per sensory neuron. In the present study, we have begun to examine which of these anatomical changes might be necessary for the maintenance of long-term sensitization by exploring the time course over which they occur and, in particular, their duration relative to the persistence of the memory assessed behaviorally. Toward this end we have quantitated changes in both the total number of varicosities and their active zone morphology in single HRP-labeled sensory neurons taken from long-term sensitized and control animals at different intervals (1–2 d, 1 week, and 3 weeks) following training. We have found that long-term sensitized animals examined within 48 hr after the completion of training demonstrate an increase in the total number of varicosities per sensory neuron as well as an increase in the incidence, size, and vesicle complement of their synaptic active zones compared with control animals. The increase in the number of varicosities and active zones persists unchanged for at least 1 week, and the increase in active zone number is only partially reversed at the end of 3 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)
Dynamics of the endoplasmic reticulum and other membranous organelles in growth cones of cultured neurons
Authors: Dailey ME , Bridgman PC
Published: March 2018

The fluorescent lipophilic dye 3,3′-dihexyloxacarbocyanine iodide [DiOC6(3)] was used to examine the distribution of membrane-bound organelles in growth cones of cultured rat sympathetic neurons. Within chemically fixed growth cones, intense DiOC6(3) fluorescence was localized predominately to the base or central region of growth cones. However, in most growth cones several thin DiOC6(3)-fluorescent processes radiated from the base into the periphery, and double fluorescence imaging of single growth cones indicated that these processes were highly colocalized (approximately 79%) with microtubules. The distribution of DiOC6(3) fluorescence in living growth cones was examined using low light-level fluorescence video microscopy. We observed thin fluorescent processes within the periphery of growth cones to undergo length excursions (extension/retraction) and to change orientation (move laterally). During growth cone advance, processes became progressively thicker and were gradually engulfed by the advancing fluorescent mass. When growth cones were viewed with video-enhanced differential interference contrast microscopy, the position of the fluorescent processes correlated with thickened extensions of central-type cytoplasm through which vesiclelike organelle transport often occurred. These observations indicate several features concerning the organization and movement of membranous organelles (MOs) in growth cones: (1) MOs are highly compartmentalized, the majority being localized to the growth cone base; (2) MOs advance into the periphery along distinct pathways probably associated with microtubules; (3) one or more thin continuous MOs, which most likely represent a thin tubular component of the endoplasmic reticulum, generally precedes advance of vesiclelike MOs along individual transport pathways; and (4) transport pathways with their associated MOs are spatially and temporally dynamic.
Naturally occurring cell death and differentiation of developing spinal motoneurons following axotomy
Authors: Farel PB
Published: March 2018

The purpose of this study was to examine the effects of axon transection on the development and differentiation of spinal motoneurons in the bullfrog (Rana catesbeiana) tadpole. The 3 ventral roots (VRs) that innervate the hindlimb were transected, and the animals were killed 6–7 weeks later (reinnervation took place within 3 weeks). At early stages of development, axotomy resulted in an increase in the number of spinal motoneurons on the operated side. By histological criteria, these motoneurons appeared more differentiated than those in normal tadpoles. Axotomy was effective in increasing motoneuron number only during the period of naturally occurring cell death. Similar effects were seen when the transected VRs were ligated to prevent regeneration. Hindlimb amputation without VR transection had no effect on motoneuron number or differentiation. Thus, target removal is neither a necessary nor a sufficient condition for hyperplasia of the lateral motor column. An extreme loss of spinal motoneurons was seen if the operated tadpole entered into metamorphic climax during the 6–7-week postoperative survival period. Motoneuron loss occurred although the injured motoneurons had reconnected to the hindlimb. In contrast, tadpoles allowed to survive up to 6 months showed no loss of motoneurons if they did not enter metamorphic climax. From these data, it appears axon transection in developing spinal motoneurons exerts its effects on motoneuron number and differentiation by altering the metabolic state of the motoneuron (axon reaction) rather than by depriving it of contact with its target.
Electron microscopic localization of neurotensin binding sites in the midbrain tegmentum of the rat. I. Ventral tegmental area and the interfascicular nucleus
Authors: Dana C , Vial M , Leonard K , Beauregard A , Kitabgi P , Vincent JP , Rostene W , Beaudet A
Published: March 2018

The distribution of specifically labeled neurotensin (NT) binding sites was examined by light and electron microscopic radioautography in the ventral tegmental area (VTA) and nucleus interfascicularis of the rat following incubation of lightly prefixed midbrain slices with the monoiodinated ligand, 125I-(Tyr3)-NT. Film radioautograms of whole 125I- NT-incubated slices exhibited intense NT displaceable binding throughout the VTA and interfascicular nucleus. In light microscopic radioautographs from 1-microns-thick sections taken from the surface of the slices, the label was found to be present both inside and outside neuronal perikarya. Probability circle analysis of silver grain distribution in electron microscopic radioautographs confirmed that a significant proportion (greater than 20%) of the specifically labeled binding sites was intraneuronal. The frequent association of these sites with profiles of rough endoplasmic reticulum or Golgi apparatus suggested that they corresponded in part to receptors undergoing synthesis and/or glycosylation. The remainder was associated with neuronal and/or glial plasma membranes, as attested by comparing the distribution of grains overlying apposed cellular elements with the distribution of hypothetical grains originating from randomly distributed membrane bound radioactive sources. Although the resolution of the technique did not make it possible to ascribe labeled membrane- bound receptors to either one of the apposed plasma membranes, their frequent association with interfaces involving the plasmalemma of perikarya and dendrites, together with the occurrence of silver grain alignments along the membrane of certain somata and dendrites suggested that a proportion of them was associated with the perikarya and dendrites of a subpopulation of ventral tegmental neurons. Interestingly, these perikaryal and dendritic receptors were not exclusively present on, or even concentrated opposite, abutting axon terminals but instead were more or less evenly distributed along the plasma membrane. Only an exceedingly small proportion was found to be associated with synaptic junctions. Such a low incidence makes it unlikely that only the synapse-linked binding sites correspond to functional receptors. On the contrary, the dispersion of labeled receptors seen here along the plasma membrane of presumptive dopamine neurons suggests that NT acts mainly in a paracrine or parasynaptic fashion in the ventral midbrain tegmentum.
Preganglionic and sensory origins of calcitonin gene-related peptide- like and substance P-like immunoreactivities in bullfrog sympathetic ganglia
Authors: Horn JP , Stofer WD
Published: March 2018

These experiments further define the organization of peptidergic pathways in the paravertebral sympathetic system of the bullfrog. Populations of axons and synaptic boutons in sympathetic ganglia 9 and 10 were found to express calcitonin gene-related peptide-like immunoreactivity (CGRP-IR) and substance P-like immunoreactivity (SP- IR). CGRP-IR is present in fibers that run through the ganglia and in boutons that make contact with almost half of the principal neurons. SP- IR is also present in fibers within the ganglia and in a rare class of synaptic boutons that are found on less than 1% of the principal neurons. Both forms of immunoreactivity are coexpressed in some nerve fibers and in the rare synaptic boutons that contain SP-IR. Neuropeptide Y-like immunoreactivity (NPY-IR), a marker for C-type postganglionic neurons, was used to identify the postsynaptic targets of boutons containing CGRP-IR and SP-IR. Ninety-five percent of the ganglion cells contacted by CGRP-IR boutons were negative for NPY-IR and are therefore likely to be B-type postganglionic neurons. Similarly, 100% of the ganglion cells contacted by boutons containing SP-IR were negative for NPY-IR. Lesions of the sympathetic chain demonstrated that synaptic boutons containing CGRP-IR arise from neurons whose axons enter the chain rostral to ganglion 7. Cutting the chain between ganglia 8 and 9 eliminates all preganglionic B and C inputs to ganglia 9 and 10. The destruction of the preganglionic C pathway by this lesion was verified by staining ganglia 9 and 10 for luteinizing hormone releasing hormone (LHRH). This lesion also eliminated boutons containing CGRP-IR and drastically reduced the number of ganglionic fibers that stained for CGRP-IR and SP-IR. By contrast, cutting the sympathetic chain between ganglia 6 and 7 spared LHRH-IR in the preganglionic C pathway but still eliminated the boutons that normally express CGRP-IR and reduced the amount of staining for SP- IR. CGRP-IR in the sympathetic ganglia arises from preganglionic and sensory neurons whereas ganglionic SP-IR is purely sensory in origin. In the spinal cord, the preganglionic B and C neurons that innervate ganglia 9 and 10 are located in different segments. In segments that contain preganglionic B cells, but not those that contain C cells, there were 243 +/- 37 (mean +/- SD) neurons in the intermediolateral cell column that express CGRP-IR. However, no cell bodies containing SP- IR were found in this region of the spinal cord.(ABSTRACT TRUNCATED AT 400 WORDS)
Dopamine transport sites selectively labeled by a novel photoaffinity probe: 125I-DEEP
Authors: Grigoriadis DE , Wilson AA , Lew R , Sharkey JS , Kuhar MJ
Published: March 2018

The dopamine transporter was labeled using a photosensitive compound related to GBR-12909, 125I-1-[2-(diphenylmethoxy)ethyl]-4-[2- (4-azido- 3-iodophenyl)ethyl]piperazine (125I-DEEP). 125I-DEEP bound reversibly and with high affinity to the dopamine transport protein in the absence of light and could be covalently attached to the protein following exposure to UV light. In rat striatal homogenates, 125I-DEEP was found to incorporate covalently into a protein with apparent molecular weight of 58,000 Da. The properties of this binding protein were characteristic of the dopamine transporter since covalent attachment could be inhibited by dopamine-uptake blockers with the proper pharmacological rank order of potencies. Covalent binding was also inhibited in a stereospecific manner by (+) and (-) cocaine, as well as other cocaine analogs. The protein was not found in the cerebellum. The dopamine transporter appears to exist in a glycosylated form since photoaffinity-labeled transport sites could adsorb to wheat germ- agglutinin and could be specifically eluted from the column by beta-N- acetylglucosamine.
Substance P receptors on canine chief cells: localization, characterization, and function
Authors: Vigna SR , Mantyh CR , Soll AH , Maggio JE , Mantyh PW
Published: March 2018

Saturable binding sites for 125I-Bolton-Hunter substance P were observed in frozen sections of the oxyntic mucosa of the canine stomach using quantitative autoradiography. The cell type possessing substance P binding sites in this region was identified as the chief cell in 2 ways. First, the saturable binding of radioiodinated substance P correlated with chief cell content (and not with parietal cell content, for example) in dispersed oxyntic mucosal cells fractionated by centrifugal elutriation. Second, saturable binding of radioiodinated substance P was localized to dispersed chief cells by autoradiography using emulsion-coated preparations of isolated cells affixed to glass slides. Parietal and mucous cells did not bind substance P. In studies of enriched chief cell preparations, the binding of radiolabeled substance P was found to be time- and cell number-dependent, specific, saturable, reversible, and of high affinity. Equilibrium binding analysis revealed a single class of binding sites with an apparent Kd of 105 pM and a Bmax of 3000 receptors per cell. In competitive displacement studies, the order of potency of analogs for inhibition of the saturable binding of radiolabeled substance P to chief cells was substance P = physalaemin greater than substance K greater than neuromedin K; thus, the chief cell has a substance P-preferring tachykinin binding site. Bombesin, cholecystokinin, and somatostatin had no effect on substance P binding. Substance P stimulated pepsinogen secretion from isolated canine oxyntic glands in dose-dependent fashion with a half-maximal response occurring at a substance P dose of about 1 mM.(ABSTRACT TRUNCATED AT 250 WORDS)
Influences of hippocampal place cell firing in the awake state on the activity of these cells during subsequent sleep episodes
Authors: Pavlides C , Winson J
Published: March 2018

Rat hippocampal (CA1) complex spike “place cells” of freely behaving rats were recorded in pairs continuously during a series of waking (exploration and still-alert), drowsy (quiet-awake), and sleeping (slow- wave, pre-rapid-eye-movement and rapid-eye-movement sleep) behaviors. Pairs of units were selected that had nonoverlapping place fields. The rats were restricted from entering the place field of either cell overnight, and on the day of recording cells were exposed to their individual place fields independently and in a counterbalanced manner. Following exposure, recordings were made in the subsequent sleep episodes and the firing characteristics of both cells were analyzed. Following exposure, significant increases in the spiking activity of the exposed cell were observed in the subsequent sleeping states that were not evident in the unexposed cell. The increased activity was observed in the rate of firing (spikes/sec), the rate of occurrence of bursts with multiple spikes, as well as the number of bursts displaying short (2–4 msec) interspike intervals. The findings suggest that neuronal activity of hippocampal place cells in the awake states may influence the firing characteristics of these cells in subsequent sleep episodes. The increased firing rates along with the greater number of multiple spike bursts and the shorter interspike intervals within the burst, following exposure to a cell's place field, may represent possible information processing during sleep.
Multiple forms of pancreatic polypeptide-related compounds in the lamprey CNS: partial characterization and immunohistochemical localization in the brain stem and spinal cord
Authors: Brodin L , Rawitch A , Taylor T , Ohta Y , Ring H , Hokfelt T , Grillner S , Terenius L
Published: March 2018

Although neuropeptide Y (NPY) is established as a transmitter in many regions of the nervous system, the role of other peptides of the pancreatic polypeptide (PP) family in the CNS is obscure. This study provides evidence that PP-like peptides in the “primitive” CNS of a cyclostome are composed of different molecular forms, which are stored in separate neuronal populations with apparently different functions. PP-like material was detected in extracts of brain and spinal cord from Lampetra fluviatilis by radioimmunoassay (RIA) using an antiserum to the C-terminal hexapeptide of mammalian PP. The PP-immunoreactive material consisted of several molecular forms, as shown by its complex elution profile on high-performance liquid chromatography (HPLC). The cellular distribution of PP-like immunoreactivity was studied with indirect immunofluorescence histochemistry using antisera toward porcine peptide YY (PYY), porcine neuropeptide Y (NPY), and bovine (BPP), rat (RPP), and avian (APP) pancreatic polypeptide. Adjacent sections from the brain stem and spinal cord of L. fluviatilis and Ichthyomyzon unicuspis, incubated with the different antisera, displayed 2 main patterns of PP immunoreactivity. The PYY and RPP antisera labeled groups of neurons and fibers in the rhombencephalic and mesencephalic reticular formation. One of the PYY/RPP-ir cell groups, located in the anterior rhombencephalic reticular nucleus, had a projection to the dorsolateral spinal cord. Fibers of this reticulospinal system were in close apposition to dendrites of intracellularly stained spinal motoneurons and sensory relay interneurons, indicating that they may receive PPergic input. In contrast, antisera to NPY and APP labeled local neurons systems in the spinal dorsal horn, in the lateral parts of the brain stem, including the rhombencephalic alar plate, and in the retina. The BPP antiserum recognized the NPY/APP as well as the PYY/RPP immunoreactive neuron systems, further supporting that they both contain PP-like peptides.
Morphology and electrophysiological properties of immunocytochemically identified rat dopamine neurons recorded in vitro
Authors: Grace AA , Onn SP
Published: March 2018

In vitro intracellular recordings were made from neurons in the rat midbrain slice. Two neuronal types could be distinguished in dopamine- containing (DA) midbrain regions based on electrophysiological criteria. One neuron type exhibited short duration action potentials (less than 1.5 msec), could fire at high frequencies (greater than 10 Hz), and exhibited either phasic or burst firing patterns. This neuron did not exhibit tyrosine hydroxylase immunoreactivity. A second neuronal type exhibited a unique set of electrophysiological properties, which included (1) a spontaneous pacemaker-like depolarizing potential, (2) a highly regular firing pattern, (3) long duration (greater than 2 msec) action potentials, and (4) a high (i.e., depolarized) spike threshold. This neuron was consistently double labeled using intracellular staining and immunocytochemical localization of the catecholamine-specific enzyme tyrosine hydroxylase, and thus represented the DA neuronal type. Midbrain DA neurons stained with Lucifer yellow could be separated into 3 classes based on their location and morphology: (1) fusiform neurons with laterally projecting dendrites in the dorsal substantia nigra zona compacta region, (2) multipolar cells with laterally and ventrally projecting dendrites in the ventral substantia nigra zona compacta, and (3) neurons with fusiform and multipolar somata and radially projecting dendrites in the ventral tegmental area. The dendrites also exhibited spine-like protrusions and ended with specialized forked processes. Spontaneously firing DA cells recorded in vitro had a number of distinguishing electrophysiological characteristics in common with those of DA neurons recorded in vivo, such as the presence of a slow depolarizing potential driving spike activity and a characteristic depolarized spike threshold (approximately-36 mV). However, in contrast to that found in vivo, the DA cells characterized here exhibited substantially higher input resistances and fired spontaneously in a very regular pacemaker pattern. Burst firing was not observed. Spike activity was apparently dependent on 4 depolarizing events: (1) a voltage-dependent TTX- sensitive slow depolarization, (2) a cobalt-sensitive low threshold depolarization that was activated during the rebound from brief membrane hyperpolarizations, (3) high threshold dendritic calcium spikes which gave rise to the spike afterhyperpolarization, and (4) a high threshold initial segment sodium spike. These depolarizations were modulated by several processes, including a 4-aminopyridine-insensitive delayed repolarization, an instantaneous and time-dependent anomalous rectifier, and an afterhyperpolarization. Although low threshold depolarizations and rebound action potentials could be triggered by the membrane repolarization following small membrane hyperpolarizations, comparatively larger hyperpolarizations attenuated this rebound activation, thereby suppressing anodal break excitation.(ABSTRACT TRUNCATED AT 400 WORDS)
Expression of growth-associated protein B-50 (GAP43) in dorsal root ganglia and sciatic nerve during regenerative sprouting
Authors: Van der Zee CE , Nielander HB , Vos JP , Lopes da Silva S , Verhaagen J , Oestreicher AB , Schrama LH , Schotman P , Gispen WH
Published: March 2018

Recently it has been shown that B-50 is identical to the neuron- specific, growth-associated protein GAP43. The present study reports on the fate of B-50/GAP43 mRNA and B-50/GAP43 protein, determined by radioimmunoassay, in a rat model of peripheral nerve regeneration (sciatic nerve crush) over a period of 37 and 312 d, respectively. Moreover, the effects of repeated subcutaneous injection of the neurotrophic peptide Org.2766 (an ACTH4–9 analog) and of a conditioning lesion on B-50/GAP43 protein levels in the regenerating nerve and dorsal root ganglia (DRG) were investigated. Both treatments enhanced the functional recovery as evidenced by a foot-flick withdrawal test. Immunocytochemical analysis using antineurofilament antibodies revealed a peptide-induced increase in the number of outgrowing sprouts in the sciatic nerve. Both the peptide and the conditioning lesion amplified the crush lesion-induced increase in B-50 protein content in the nerve as determined by radioimmunoassay. B-50 protein levels seem to correlate proportionally with the number of sprouts. In the DRG of the crushed sciatic nerve, the time course of B-50 expression was studied. B-50 mRNA was quantified from Northern blots. A linear increase up to 10 times the basal level of B-50 mRNA was observed 2 d postsurgery, followed by a gradual decline to normal levels at day 37. The first significant rise in B-50 mRNA level became apparent between 8 and 16 hr after placement of the crush lesion. The first significant rise in B-50 protein level occurred 40 hr after the crush lesion, reaching a plateau of 3 times the basal level between day 6 and 20. B-50 protein levels in DRG cell bodies remained elevated up to 60 d after crush, a period much longer than that observed for B-50 mRNA. Thus, during a later phase of peripheral axonal regeneration, the presence of B-50 appears to be prolonged, probably by an increase in half-life and not so much by enhanced transcription. Treatment with Org.2766 did not affect the B- 50/GAP43 levels in DRG cell bodies during the first 6 d following crush. Conditioning lesion resulted in a DRG B-50/GAP43 protein amount at the same level as in rats 14 d after the test lesion. B-50/GAP43 levels in DRG are probably influenced by the rapid axonal transport of the protein, as has been reported by others.
Multiple effects of phorbol esters in the rat spinal dorsal horn
Authors: Gerber G , Kangrga I , Ryu PD , Larew JS , Randic M
Published: March 2018

Spinal cord slice preparation and intracellular recording techniques were used to examine the effects of phorbol esters on the sodium- and calcium-dependent action potentials, the excitatory synaptic transmission, the basal (resting) and the dorsal root stimulation- evoked release of 9 endogenous amino acids, including glutamate and aspartate, and the responsiveness of the rat dorsal horn neurons to excitatory amino acids (glutamic, kainic, quisqualic, and N-methyl-D- aspartic). 4-beta-Phorbol-12, 13-dibutyrate and 4-beta-phorbol-12, 13- diacetate produced minor alterations in membrane potential and resistance, but they broadened the sodium-dependent action potential and reduced the duration of the calcium-dependent action potential. In addition, phorbol esters caused a marked and long-lasting increase in the amplitude and the duration of excitatory postsynaptic potentials (EPSPs) evoked in dorsal horn neurons by orthodromic stimulation of a lumbar dorsal root. Phorbol esters produced a brief increase in the basal and electrically evoked release of endogenous excitatory (glutamic, aspartic) and inhibitory amino acids (glycine, GABA). In addition, the rates of release of alanine, serine, and threonine were also elevated. In the presence of TTX, phorbol esters selectively enhanced, in a reversible manner, the depolarizing responses of dorsal horn neurons to N-methyl-D-aspartic acid and L-glutamate but not the responses to kainic or quisqualic acids. The potentiation of the NMDA response was blocked by APV, a specific NMDA receptor antagonist. Thus, phorbol esters appear to enhance excitatory synaptic transmission in the rat spinal dorsal horn slice preparation by acting both at pre- and postsynaptic sites. Phorbol esters could potentiate excitatory synaptic transmission by acting predominantly at a postsynaptic site (NMDA receptor), since the duration of the increased responsiveness of dorsal horn neurons to glutamate and NMDA correlates better with the enhancement of EPSPs than with the increased release of the stimulation- evoked glutamate and aspartate. The increased release of endogenous amino acids is consistent with a presynaptic (terminal) site of action, but it could also be explained by enhanced interneuronal activity. Although our results suggest that in the rat spinal dorsal horn protein kinase C may have a role in controlling the release of putative excitatory and inhibitory neurotransmitters and may also be involved in the regulation of postsynaptic NMDA receptors, the identity of endogenous substance(s) participating in these effects is presently unknown.
Nondopaminergic prefrontocortical efferent fibers modulate D1 receptor denervation supersensitivity in specific regions of the rat striatum
Authors: Herve D , Trovero F , Blanc G , Thierry AM , Glowinski J , Tassin JP
Published: March 2018

A unilateral injection of 6-OHDA (6 microgram/1.5 microliter) was made into the fields of Forel in order to estimate the effects of the destruction of ascending dopaminergic (DA) pathways on the denervation supersensitivity of DA D1 receptors in the rat striatum. DA-sensitive adenylate cyclase activity was markedly enhanced in the anteromedian part of the striatum 3 weeks after the lesion (+68%) and remained elevated for several weeks thereafter (+36%). A different response occurred in the laterodorsal striatum, where the increase in DA- sensitive adenylate cyclase activity was less pronounced after 3 weeks (+40%) and no longer present after 7 weeks. Estimations of catecholamine levels indicated that the lesion made destroyed not only nigrostriatal DA neurons but other ascending catecholaminergic fibers projecting into the cerebral cortex as well. In addition, retrograde transport experiments made with wheat germ agglutinin coupled to horseradish peroxidase indicated that the anteromedian part of the striatum, but not the laterodorsal one, receives both an ipsi- and contralateral cortical projection originating in the prefrontocortical DA field. When the destruction by 6-OHDA of this contralateral DA innervation was combined to the unilateral lesion of the fields of Forel, the increase in DA-sensitive adenylate cyclase activity in each striatal area 3 or 7 weeks postlesion was prevented. This effect was due to DA denervation of the prefrontal cortex since striatal D1 denervation supersensitivity was still observed when contralateral ascending noradrenergic fibers were selectively destroyed by a 6-OHDA lesion made laterally to the pedunculus cerebellaris superior. These results suggest that, by controlling the activity of corticostriatal neurons, the mesocorticoprefrontal DA neurons exert a permissive role on the development of D1-receptor denervation supersensitivity in specific areas of the striatum.
Riluzole, a novel antiglutamate, prevents memory loss and hippocampal neuronal damage in ischemic gerbils
Authors: Malgouris C , Bardot F , Daniel M , Pellis F , Rataud J , Uzan A , Blanchard JC , Laduron PM
Published: March 2018

The neuroprotective effects of riluzole, a novel antiglutamate, has been demonstrated in a model of ischemia induced in female Mongolian gerbils by transient bilateral carotid occlusion. Riluzole was administered at a dose of 4 mg/kg, i.p., just before, 4 hr after, and for the 14 d following the transient bilateral carotid occlusion (10 min). The functional sequelae of ischemic damage were assessed using a memory test (passive avoidance) and the extent of neuronal damage by histological examination and quantitative autoradiography of muscarinic cholinergic receptors in the hippocampus. The performance of the ischemic gerbils in the memory test was about half that of control animals. This memory deficit was completely reversed in animals treated with riluzole. This protective effect of riluzole was confirmed by histological and autoradiographic studies. The neuronal degeneration of CA1 pyramidal cells in the hippocampus observed in the ischemic group was not seen in the riluzole-treated animals, which resembled the control group. This neuronal degeneration in the CA1 area was confirmed by a quantitative measurement of muscarinic receptors: The binding was decreased by a third in the lacunosum moleculare, the stratum oriens, and the stratum radiatum. By contrast in riluzole-treated gerbils, this decrease was reversed by 50%. Finally, a clear-cut correlation was found between the deficit in the memory test and the decrease in muscarinic receptor binding in the CA1 fields. These results are compatible with the idea that glutamic acid may be involved in the neuronal degeneration of the hippocampus following ischemia, and could be foreseeable.(ABSTRACT TRUNCATED AT 250 WORDS)
Regulation of tension on hair-cell transduction channels: displacement and calcium dependence
Authors: Hacohen N , Assad JA , Smith WJ , Corey DP
Published: March 2018

An epithelial preparation of the bullfrog sacculus was used to characterize the initial rate of the adaptation mechanism in hair cells and its dependence on displacement and calcium. The I(X) curve relating transduction current and bundle displacement shifted along the X-axis without substantial change in slope, as previously observed, suggesting that adaptation involves a change in the attachment point of the elastic element connected to ion channels. If the “tip links” model of transduction is correct, this implies that one end of the link moves along the side of the stereocilium. The rates were highly asymmetric: in the tensioning direction the rate was roughly constant at 1– microns/sec (calculated as motion along a stereocilium); this is similar to that of myosin on actin. In the relaxing direction it appeared linearly dependent on tension. Calcium preferentially potentiated the relaxation, and apparently reduced the resting tension in the elastic element. The calcium site appears specific for calcium, as other divalent cations inhibited its action. Dihydrostreptomycin inhibited the positive rate, but its effect could not be explained by a simple channel block, and it seems inconsistent with screening of negative charge in the mouth of the transduction channel.
Elevated cytosolic calcium in the growth cone inhibits neurite elongation in neuroblastoma cells: correlation of behavioral states with cytosolic calcium concentration
Authors: Silver RA , Lamb AG , Bolsover SR
Published: March 2018

Schubert (1984) and Kater et al. (1988) have suggested that motility and growth at the neuronal growth cone is activated by an increase of cytosolic free calcium concentration ([Ca2+]i) above the levels found in quiescent growth cones. In order to test this model, we have used a digital imaging fluorescence microscope together with injection of the fluorescent indicator dye Fura-2 to measure [Ca2+]i in growth cones of a mammalian sympathetic neuron, the N1E-115 neuroblastoma cell. The behavior of individual growth cones, together with spontaneously varying levels of [Ca2+]i within the growth cone, were monitored for periods of up to several hours. [Ca2+]i in motile, advancing growth cones was low and equal to [Ca2+]i in quiescent growth cones. Higher values of [Ca2+]i were found in motile growth cones that were not advancing, suggesting that a small elevation of [Ca2+]i inhibits neurite extension. A further rise of [Ca2+]i above the level found in motile, nonadvancing growth cones appeared to inhibit motility and cause retraction of the growth cone back towards the cell body. Spatial gradients of [Ca2+]i within the growth cone were small and, where statistically significant, [Ca2+]i was lower by 5–10 nM in motile regions. Our results are incompatible with the model that a rise of [Ca2+]i is responsible for activating quiescent growth cones; however, our results suggest that in active growth cones [Ca2+]i can regulate morphology and behavior.
Identified facilitator neurons L29 and L28 are excited by cutaneous stimuli used in dishabituation, sensitization, and classical conditioning of Aplysia
Authors: Hawkins RD , Schacher S
Published: March 2018

Tactile or electrical stimulation of the skin can be used to produce dishabituation, sensitization, and classical conditioning of the gill- and siphon-withdrawal reflex in Aplysia. These behavioral effects are thought to involve presynaptic facilitation at the synapses from siphon sensory neurons to gill and siphon motor neurons. Facilitation of PSPs onto the motor neurons can also be produced by intracellular stimulation of single identified neurons in the abdominal ganglion, including L29 and L28. In this paper, we further characterize L29 and L28. First, we show that they are excited by cutaneous stimuli similar to those used to produce dishabituation, sensitization, and classical conditioning and may therefore participate in mediating those behavioral effects. The results are also consistent with a possible role of L29 and L28 in higher-order features of conditioning. Second, we show that 5-HT does not mimic some of the PSPs of L29, in agreement with previous evidence that L29 is not serotonergic. Third, we present 2 types of evidence that L29 acts directly to produce facilitation of the sensory cells: (1) L29 comes into close contact with sensory cells in fluorescent double-labeling experiments, and (2) L29 produces facilitation of sensory cells in dissociated cell culture. Together with the results of the preceding paper (Mackey et al., 1989), these results indicate that facilitation of sensory cell synapses contributing to behavioral enhancement of the reflex can be produced by identified neurons that use 2 different transmitters: 5-HT (the transmitter of CB1) and the unknown transmitter of L29.
Task-dependent field potentials in human hippocampal formation
Authors: McCarthy G , Wood CC , Williamson PD , Spencer DD
Published: March 2018

Task-dependent field potentials were recorded from implanted electrodes located in the hippocampus and other medial temporal lobe (MTL) structures of epileptic patients undergoing evaluation for possible surgery. In 2-alternative categorization tasks, low-probability auditory, somatic, and visual stimuli elicited potentials with large amplitudes and sharp spatial gradients having the following characteristic spatial distribution: positive posterior to the hippocampus, negative within the hippocampus, and positive anterior to the hippocampus. The sharp spatial gradients within the MTL suggest that these potentials were locally generated, probably by hippocampal pyramidal cells. The MTL potentials were also reliably elicited by exemplars of semantic categories and by stimulus omissions and were sensitive to the sequence of preceding stimuli. However, they were not elicited by the same stimulus sequences when the patient's attention was directed elsewhere and categorization was not required. These results indicate that the MTL potentials reflect endogenous as opposed to obligatory processes. The time course and task dependence of the MTL potentials suggest that MTL structures could contribute to P300 and related event-related potentials on the scalp.
Organized arrangement of orientation-sensitive relay cells in the cat's dorsal lateral geniculate nucleus
Authors: Shou TD , Leventhal AG
Published: March 2018

We studied the physiological orientation biases of over 700 relay cells in the cat's dorsal lateral geniculate nucleus (LGNd). Relay cells were sampled at regular intervals along horizontally as well as vertically oriented electrode penetrations in a fashion analogous to that used previously in studies of visual cortex (Hubel and Wiesel, 1962). The strengths of the orientation biases and the distributions of the preferred orientations were determined for different classes of relay cells, relay cells in different layers of the LGNd, and relay cells subserving different parts of the visual field. We find that, at the population level, LGNd cells exhibit about the same degree of orientation bias as do the retinal ganglion cells providing their inputs (see also Soodak et al., 1987). Also, as in the retina (Levick and Thibos, 1982; Leventhal and Schall, 1983), most LGNd cells tend to prefer stimuli oriented radially, i.e., parallel to the line connecting their receptive fields to the area centralis projection. However, the radial bias in the LGNd is weaker than in the retina. Moreover, there is a relative overrepresentation of cells preferring tangentially oriented stimuli in the LGNd but not in the retina. As a result of the overrepresentation of cells preferring radial and tangential stimuli, the overall distribution of preferred orientations varies in regions of the LGNd subserving different parts of the visual field. Reconstructions of our electrode penetrations provide evidence that, unlike in the retina, cells having similar preferred orientations are clustered in the LGNd. This clustering is apparent for all cell types and in all parts of laminae A and A1. The tendency to cluster according to preferred orientation is evident for cells preferring radially, intermediately, and tangentially oriented stimuli and thus is not simply a reflection of the radial bias evident among retinal ganglion cells at the population level. It is already known that cells having inputs from different eyes, on-center, off-center, X-, Y-, W-type, and color-sensitive ganglion cells are distributed nonrandomly in the LGNd of cats and monkeys (for review, see Rodieck, 1979; Stone et al., 1979; Lennie, 1981; Stone, 1983). The finding that relay cells having similar preferred orientations are also distributed nonrandomly suggests that the initial sorting of virtually all properties segregated in visual cortex may begin in the LGNd.
The projection from medial geniculate to field AI in cat: organization in the isofrequency dimension
Authors: Brandner S , Redies H
Published: March 2018

The topography of the anatomical projection from isofrequency contours (IFCs) in auditory thalamus to IFCs in primary auditory cortex (field AI) was investigated in the cat. In each experiment, a best-frequency map of AI was obtained with electrophysiological recording techniques. Then, different retrogradely transported tracers (HRP, fluorescent dyes) were introduced into AI. In some experiments, different parts (e.g., dorsal, central, and ventral) of a previously mapped IFC were injected, each part with a different tracer. In other experiments, 2 or 3 rows of tracer injections were made at different dorsoventral levels of AI, over a large frequency range (5–38 kHz); each injection row was oriented orthogonal to the IFCs and contained a different tracer. The main mass of the labeled thalamic cells was found in the ventral nucleus of the medial geniculate body (MGv). The MGv cells projecting to a limited sector (1–2 mm in length in most experiments) of an IFC in AI form one or several densely packed neuron clusters of variable shape. The cells labeled by a given tracer are largely separated in space from cells labeled by a different tracer. Thus, different sectors of a cortical IFC receive input from different portions of the corresponding thalamic IFC. As a general rule, cells labeled from dorsal (ventral) injections are centered rostrally (caudally) in the part of MGv innervating AI. However, the topographic details are variable between individuals, and the rostrocaudal gradient is complicated by numerous irregularities and gradients. Previous studies of the auditory thalamocortical projection in the cat have not recognized the topographic order in the isofrequency dimension. Instead, it was believed that different sectors of a cortical IFC were innervated by coincident thalamic populations.
Phospholipase A2 and 3H-hemicholinium-3 binding sites in rat brain: a potential second-messenger role for fatty acids in the regulation of high-affinity choline uptake
Authors: Saltarelli MD , Yamada K , Coyle JT
Published: March 2018

The involvement of phospholipase A2 (PLA2) and fatty acid release in the regulation of sodium-dependent high-affinity choline uptake in rat brain was assessed in vitro through the use of the specific binding of 3H-hemicholinium-3 (3H-HCh-3). Addition of arachidonic acid and other unsaturated fatty acids to rat striatal membranes in vitro resulted in a dose-dependent, temperature-independent activation of 3H-HCh-3 binding. Scatchard analysis revealed that these changes in binding result from a 2-fold increase in the affinity and capacity of 3H-HCh-3 binding. Saturated fatty acids, lysophospholipids, and phospholipids did not affect specific 3H-HCh-3 binding. Addition of defatted BSA to membranes, which had been treated previously with arachidonic acid, completely reversed the increase in specific 3H-HCh-3 binding. However, several inhibitors of fatty acid metabolism, including nordihydroguaiaretic acid, indomethacin, catalase, and superoxide dismutase, did not alter arachidonic acid-induced changes in 3H-HCh-3 binding, suggesting that unsaturated fatty acids, and not their metabolites, are directly responsible for the observed activation of specific 3H-HCh-3 binding. Additionally, unsaturated fatty acids dose- dependently inhibited high-affinity 3H-choline uptake in rat striatal synaptosomes, apparently due to the disruption of synaptosomal integrity. The phospholipase A2 inhibitors quinacrine hydrochloride, trifluoperazine, and 4-bromophenacylbromide dose-dependently inhibited potassium depolarization-induced activation of specific 3H-HCh-3 binding in slices of rat brain in vitro. Similarly, both quinacrine and trifluoperazine inhibited the metabolism of phospholipids and the release of fatty acids evoked by either elevated KCl or calcium ionophore A23187. These results support the involvement of PLA2 and subsequent fatty acid release in the increase of 3H-HCh-3 binding in cholinergic neurons and suggest that activation of PLA2 may be the penultimate step in regulating the velocity of sodium-dependent choline transport.
Neurotransmitter modulation of calcium current in rat spinal cord neurons
Authors: Sah DW
Published: March 2018

The modulation of Ca2+ currents by neurotransmitters was studied in freshly dissociated rat spinal cord neurons, using the whole-cell patch- clamp technique. GABA, baclofen, adenosine, ATP, serotonin, norepinephrine, somatostatin, and dynorphin A inhibited the current through Ca2+ channels in a substantial fraction of cells, while substance P, vasoactive intestinal polypeptide, [D-ala2,d-leu5]- enkephalin, cholecystokinin-8 (sulfated), calcitonin gene-related peptide, angiotensin II, neurotensin, vasopressin, and thyrotropin- releasing hormone had no effect. In the case of baclofen, the inhibition is mediated, at least in part, by a GTP-binding protein. Suppression of Ca2+ current by neurotransmitters may represent a mechanism of presynaptic inhibition in the spinal cord.