bluuebunny/crossref_metadata_2025_split huggingface dataset:
Widespread and Developmentally Regulated Expression of Neurotrophin‐4 mRNA in Rat Brain and Peripheral Tissues
Authors: Timmusk Tõnis , Belluardo Natale , Metsis Madis , Persson Håkan 
Published: April 2006

AbstractThe neurotrophin gene family includes four structurally related proteins with neurotrophic activities. Two of them, nerve growth factor and brain‐derived neurotrophic factor (BDNF), have been studied in detail and information has recently emerged on the expression and function of the third member, neurotrophin‐3. In contrast, little information is available on neurotrophin‐4 (NT‐4), the most recently isolated member of this family. In this report we have used a sensitive RNAase protection assay to analyse the developmental expression of NT‐4 mRNA in the rat brain and in 12 different rat peripheral organs. In heart, liver and muscle plus skin NT‐4 mRNA levels were maximal at embryonic day (E) E13 (the earliest time point tested), with reduced levels at later times of development. In lung, kidney and thymus similar levels were seen from E13 to postnatal day (P) 1, with reduced levels in the adult. In testis, ovary and salivary gland NT‐4 mRNA was detected at E16 with a peak shortly after birth. During brain development, NT‐4 mRNA was maximal at E13 followed by a decrease around birth, after which the level increased. The postnatal increase of NT‐4 mRNA was also seen in cerebral cortex and brain stem analysed separately, while in the hippocampus similar levels were found from P1 to adulthood. NT‐4 mRNA was detected in all ten adult rat brain regions analysed with only small regional variations, being highest in pons–medulla, hypothalamus, thalamus and cerebellum. Adult rat thymus, thyroid, muscle, lung and ovary contained higher levels of NT‐4 mRNA than brain, while all other adult tissues showed similar or lower levels than in the brain. The highest level of NT‐4 mRNA overall was found in P1 testis. For comparison, BDNF mRNA was analysed in the same tissues. The expression of BDNF mRNA was in many cases different from that of NT‐4 mRNA. The peak of NT‐4 mRNA expression in several of the peripheral tissues coincided with the peak of naturally occurring neuronal cell death in peripheral ganglia. This is consistent with the possibility that NT‐4 acts as a target‐derived trophic factor in vivo. The widespread and increased expression of NT‐4 mRNA during postnatal brain development could reflect a trophic role of NT‐4 for central nervous system neurons. However, non‐neuronal functions of NT‐4 are also possible, particularly in male and female reproductive tissues, where the NT‐4 protein could function as a growth factor for immature germ cells.
An Abundant mRNA of the Embryonic Brain Persists at a High Level in Cerebellum, Hippocampus and Olfactory Bulb During Adulthood
Authors: Studler Jeanne‐Marie , Glowinski Jacques , Lévi‐Strauss Matthieu 
Published: April 2006

AbstractIn order to identify markers of the two neuronal populations which are successively involved in forebrain ontogenesis, we performed a differential screening of a murine cDNA library with two radiolabelled probes corresponding to striatal mRNAs extracted at embryonic day (E) 17 and E20, i.e. before and after the invasion of the striatum by the late‐born matrix neurons. One of the selected clones, the 3.1 cDNA, corresponds to a very abundant embryonic neuronal transcript enriched in the germinal zones at E17 and in superficial cortical layers and striatum at E20, suggesting that it is expressed mainly in neurons belonging to a late migration wave. During adulthood, it persists at a high level in the granular layer of the cerebellum, the hippocampus and the olfactory bulb, which are the sites of postnatal neurogenesis and intense synaptic plasticity. This 2000 base RNA is enriched in polysomal fractions and encodes a small putative 68 amino acid polypeptide which is conserved in mouse and man.
Urokinase‐type Plasminogen Activator Expression by Neurons and Oligodendrocytes During Process Outgrowth in Developing Rat Brain
Authors: Dent M. A. R. , Sumi Y. , Morris R. J. , Seeley P. J. 
Published: April 2006

AbstractThe expression of tissue‐ and urokinase‐type plasminogen activators has been studied in developing cerebellum, hippocampus, cerebral cortex, olfactory bulb and olfactory mucosa of the rat by in situ hybridization. All identifiable neurons express urokinase mRNA from an early stage in their development, and this expression appears to coincide with the onset of axogenesis. For cerebellar granule cells, both axonal growth and urokinase expression are initiated before they migrate from the external granule layer; for the majority of neocortical neurons, however, both processes are commenced after the cells have migrated to the cortical plate. Neurons continue to express this protease in the adult. The large projection neurons exhibit the highest levels of message, the smaller interneurons having much lower levels except for hippocampal granule cells, which have notably high levels of expression. Glial cells generally do not express urokinase message, except for transient expression by oligodendrocytes in developing fibre tracts during the period of myelination. Thus for both neurons and oligodendrocytes, the onset of urokinase‐type plasminogen activator expression coincides with their initiation of major process outgrowth, although neurons maintain this expression in the adult, possibly to retain a degree of synaptic plasticity. In contrast, although high levels of message for the related protease, tissue plasminogen activator, are found in the embryonic floor plate, in postnatal brain it is abundantly expressed only by ventricular ependymal cells and by cells in connective tissue surrounding the olfactory nerve.
Spatiotemporal Distribution of Ca2+ Following Axotomy and Throughout the Recovery Process of Cultured Aplysia Neurons
Authors: Ziv Noam E. , Spira Micha E. 
Published: April 2006

AbstractThis study investigates the alterations in the spatiotemporal distribution pattern of the free intracellular Ca2+ concentration ([Ca2+]i) during axotomy and throughout the recovery process of cultured Aplysia neurons, and correlates these alterations with changes in the neurons input resistance and trans‐membrane potential. For the experiments, the axons were transected while imaging the changes in [Ca2+]i with fura‐2, and monitoring the neurons’resting potential and input resistance (Ri) with an intracellular microelectrode inserted into the cell body. The alterations in the spatiotemporal distribution pattern of [Ca2+]i were essentially the same in the proximal and the distal segments, and occurred in two distinct steps: concomitantly with the rupturing of the axolemma, as evidenced by membrane depolarization and a decrease in the input resistance, [Ca2+]i increased from resting levels of 0.05 – 0.1 μM to 1 – 1.5 μM along the entire axon. This is followed by a slower process in which a [Ca2+]i front propagates at a rate of 11 – 16 μm/s from the point of transection towards the intact ends, elevating [Ca2+]i to 3 – 18 μM. Following the resealing of the cut end 0.5 – 2 min post‐axotomy, [Ca2+]i recovers in a typical pattern of a retreating front, travelling from the intact ends towards the cut regions. The [Ca2+]i recovers to the control level 7 – 10 min post‐axotomy. In Ca2+‐free artificial sea water (2.5 mM EGTA) axotomy does not lead to increased [Ca2+]i and a membrane seal is not formed over the cut end. Upon reperfusion with normal artificial sea water, [Ca2+]i is elevated at the tip of the cut axon and a membrane seal is formed. This experiment, together with the observations that injections of Ca2+, Mg2+ and Na+ into intact axons do not induce the release of Ca2+ from intracellular stores, indicates that Ca2+ influx through voltage gated Ca2+ channels and through the cut end are the primary sources of [Ca2+]i following axotomy. However, examination of the spatiotemporal distribution pattern of [Ca2+]i following axotomy and during the recovery process indicates that diffusion is not the dominating process in shaping the [Ca2+]i gradients. Other Ca2+ regulatory mechanisms seem to be very effective in limiting these gradients, thus enabling the neuron to survive the injury.
Functional Consequences of a Single Nerve Growth Factor Administration Following Septal Damage in Rats
Authors: Pallage Viviane , Knusel Beat , Hefti Franz , Will Bruno 
Published: April 2006

AbstractThis study examined how possible nerve growth factor (NGF)‐induced behaviour changes after septal damage might be modulated by the lesion extent, the dose of NGF administered and the delay between surgery and the onset of testing. In a first experiment, young rats which received electrolytic septal lesions of high or low intensity (inducing respectively large and mild lesions) were treated with 10 or 30 μg NGF administered intrahippocampally in a single injection. They were tested 4 months postoperatively for open field ambulation, spontaneous alternation and radial maze performance. It was observed that irrespective of the severity of the lesions rats were impaired in the spontaneous alternation and radial maze tests; however, no obvious changes appeared in the open field test. While an NGF injection did not affect behavioural performances in rats with large lesions, it was capable of ameliorating behavioural deficits in the spontaneous alternation and radial maze tests of rats with mild lesions in both NGF dosage groups. It was also seen that lesions produced a general decrease in hippocampal choline acetyltransferase (ChAT) activity, which was not significantly affected by an NGF administration. There was no significant correlation between ChAT activity and behavioural performance of NGF‐treated rats. In a second experiment, young rats received mild septal lesions and were treated with 10 μg NGF. These rats were tested 2 weeks postoperatively for radial maze performance. NGF rats exhibited similar behaviour to controls with regard to all of the variables measured. The present results suggest that a single NGF administration spares some abilities to use spatial information efficiently providing lesions are partial.
Recovery of Brightness Discrimination in Adult Rats despite Progressive Loss of Retrogradely Labelled Retinal Ganglion Cells after Controlled Optic Nerve Crush
Authors: Sautter Jürgen , Sabel Bernhard A. 
Published: April 2006

AbstractRestoration of brightness discrimination was studied in adult rats after controlled crush of the optic nerve in order to further characterize a recently introduced experimental brain injury model. Mild, moderate or severe crush of the optic nerve produced partial or complete loss of the ability to perform a brightness discrimination task. Two to three weeks following mild injury we observed nearly complete spontaneous behavioural recovery whereas recovery was more limited after moderate and totally absent after severe crush. Horseradish peroxidase (HRP) injected into the superior colliculus was transported retrogradely across the lesion site and accumulated in retinal ganglion cells (RGCs). Two days following mild, moderate or severe crush, 28, 23 and 8% respectively of RGCs were found to be labelled with HRP, indicating that they are still connected with their target and are therefore presumably intact. RGC loss affected all areas of the retina homogeneously. At postoperative day 14, the number of morphologically‘intact’RGCs declined even further to 11% in the mild injury group, despite our observation of recovery of vision to near‐normal levels. The mechanism whereby such impressive neuronal plasticity is achieved despite the rather small number of intact RGCs is still unknown. However, further studies of the crush model using additional behavioural, morphological and electrophysiological techniques may allow us to determine more clearly the biological basis of recovery of function after central nervous system injury.
The Mode of Activation of a Barrel Column: Response Properties of Single Units in the Somatosensory Cortex of the Mouse upon Whisker Deflection
Authors: Welker E. , Armstrong‐James M. , Van der Loos H. , Kraftsik R. 
Published: April 2006

AbstractResponse properties of single units in the mouse barrel cortex were studied to determine the sequence in which the neurons that form a cortical column become activated by a single‘natural’stimulus. Mice (n= 11) were anaesthetized with urethane. For a total of 153 cells, grouped by cortical layer, responses to a standardized deflection of a single whisker were characterized using poststimulus time and latency histograms. Usually, for each unit, data were collected for stimulation of its principal whisker (PW; the whiskers corresponding to the barrel column in which the cell was located) and of the four whiskers surrounding the PW. In all layers, PW stimulation evoked responses at shorter latency than surround whisker stimulation. In layers II – III and IV a bimodal distribution of cells according to latency to PW stimulation was found. Statistical analysis indicated the presence of two classes of cells in each of these layers:‘fast’units (latency < 15 ms) and 'slow’units (latency >15 ms). The great majority of cells in layers I, V and VI fired at latencies of >20 ms to PW stimulation. In general, stimulation of surround whiskers evoked a smaller response than PW stimulation. The fast cells of layer IV showed the greatest response to PW stimulation (mean = 1.78 spikes/100 ms poststimulus). Their firing was maximal during the 10–20 ms poststimulus epoch, while the slow layer IV cells fired maximally during the 20 – 30 ms poststimulus epoch. Surround inhibition occurred in all layers within the first 10 ms after stimulus onset, during which period the fast cells are the most active ones, and are thus likely to be responsible for the surround inhibition. This notion is supported by an analysis of spike duration that showed that eight of the ten cells with a thin spike (supposed to be GABAergic; McCormick et al., J. Neurophysiol., 54, 782 – 806, 1985), had PW latencies of <15 ms. We conclude that the activation of a barrel column is initially inhibitory in nature.
The Effects of Periaqueductally Injected Transmitter Antagonists on Forebrain‐elicited Vocalization in the Squirrel Monkey
Authors: Jürgens U. , Lu C.‐L. 
Published: April 2006

AbstractIn 15 squirrel monkeys, vocalization‐eliciting electrodes were implanted into the following forebrain structures: anterior cingulate cortex, genu of the internal capsule, amygdala, bed nucleus of the stria terminalis, hypothalamus, midline thalamus, inferior thalamic peduncle and periventricular grey. Then, injections of 29 transmitter antagonists were made into the midbrain periaqueductal grey (PAG) and their effects tested on the elicitability of vocalization from the forebrain. Vocalization could be blocked completely with glutamate antagonists. NMDA receptor antagonists as well as kainate/quisqualate receptor antagonists were effective. Facilitatory effects, i.e. a decrease in threshold of forebrain‐elicited vocalization, was obtained with GABA‐A receptor, glycine and opioid antagonists. The facilitatory effect of the opioid antagonist naloxone was limited to vocalizations expressing aversive emotional states. GABA‐A receptor antagonists not only facilitated forebrain‐induced vocalization but also produced vocalization themselves, i.e. without concomitant forebrain stimulation. No effects were obtained with antagonists of muscarinic and nicotinic receptors, with the GABA‐B receptor antagonist phaclofen and antagonists of the monoamines dopamine, noradrenaline, adrenaline, serotonin and histamine. It is concluded that the PAG represents a crucial relay station of the vocalization‐controlling system. In this station, transmission of vocalization‐relevant information depends upon the activation of glutamatergic synapses. Inhibitory control is exerted by GABA, glycine and endogenous opioids. Acetylcholine, dopamine, noradrenaline, adrenaline, serotonin and histamine may play a transient modulatory role; forebrain‐induced vocalization, however, does not depend upon the cholinergic or monoaminergic activation of PAG neurons.
Interactions of Dopamine with Glutamate‐ and GABA‐mediated Synaptic Transmission in the Rat Entorhinal Cortex In Vitro
Authors: Pralong E. , Jones R. S. G. 
Published: April 2006

AbstractWe have studied the interactions between dopamine and glutamate‐mediated transmission in the entorhinal cortex using intracellular recording in a slice preparation from the rat brain. High concentrations (0.1 – 1 mM) of dopamine had weak, direct effects on the membrane potential with predominantly hyperpolarizing responses in layer II neurons and depolarizing responses in layer V. Studies with the dopamine antagonists sulpiride (D2 antagonist, 10 – 50 μM) and SCH‐23390 (D1 antagonist, 50 μM) indicated that the hyperpolarization by dopamine could be mediated by D2 receptors, although the pharmacology was not clear‐cut. The depolarizing response was not affected by either D1 or D2 antagonists. Synaptic responses of layer II and layer V cells were complex, consisting of both inhibitory and excitatory potentials. In untreated slices, dopamine reduced all components of the synaptic responses. However, when components of the responses were pharmacologically isolated, only the excitatory, glutamate‐mediated potentials were consistently affected and the GABAergic inhibitory potentials were more resistant to reduction by dopamine. Excitatory potentials mediated by both N‐methyl‐d‐aspartate and α‐amino‐3‐hydroxy‐5‐methyl‐isoxazolepropionic acid receptors were reduced by dopamine, but the former were more strongly affected. Studies with antagonists suggested that the D1 receptor is more likely to be involved in the decrement of glutamate transmission. Thus, dopamine appears to modulate glutamate‐mediated synaptic transmission in the entorhinal cortex, and it is conceivable that a disturbance in this interaction could be involved in the aetiology of schizophrenia.
Positive and Negative Brain Zones in the Snail
Authors: Balaban Pavel M. , Maksimova Olga A. 
Published: April 2006

AbstractFine wire electrodes were surgically implanted in two regions of the brain of the snail Helix aspersa. To receive electrical stimulation of the brain, a tethered snail was required to displace the end of a rod. Self‐stimulation delivered to the parietal ganglion resulted in non‐repetition of the operant response, whereas self‐stimulation delivered to the mesocerebrum resulted in an increase in response frequency. The reinforcing effect of local extracellular stimulation of two brain zones was investigated in a semi‐intact preparation of a closely related species with an identical cellular map (H.lucorum). It was found that mesocerebral stimulation increased the frequency of the reinforced spontaneous movement, but decreased the frequency of the same movement if its absence was reinforced. These results allow us to attribute positive reinforcing effects to this brain area, which is involved in the control of sexual behaviour. Different results were obtained by contingent stimulation of the rostral part of the parietal ganglia, where giant cells controlling avoidance behaviour are located. Stimulation of this zone resulted in a decrease in the frequency of the ongoing spontaneous movements. These findings make possible intracellular investigations of the mechanisms of positive and negative reinforcement.
Failure to Induce Long‐term Depression by an Anti‐Correlation Procedure in Area CA1 of the Rat Hippocampal Slice
Authors: Paulsen O. , Li Y.‐G. , Hvalby Ø. , Andersen P. , Bliss T. V. P. 
Published: April 2006

AbstractWe have independently in our two laboratories re‐examined the report by Stanton and Sejnowski (Nature, 339, 215 – 218, 1989) that single stimuli to a test pathway in area CA1 of the hippocampal slice, when delivered between short bursts of stimuli to a second, convergent pathway, produce an associative long‐term depression (LTD) in the test pathway. While robust associative LTP was observed when stimuli to the two inputs were correlated in time, the anti‐correlation procedure failed to induce LTD; rather, a trend towards potentiation was observed. This result was obtained using both submerged and interface chambers, and in two different strains of rat. A transient depression lasting for a few minutes could usually be elicited by strong tetanic stimulation; this depression was not restricted to activated pathways.
Role of Voltage‐gated Ca2+ Channels and Intracellular Ca2+ in Rat Sympathetic Neuron Survival and Function Promoted by High K+ and Cyclic AMP in the Presence or Absence of NGF
Authors: Murrell Ruth D. , Tolkovsky Aviva M. 
Published: April 2006

AbstractWe have examined how NGF‐dependent rat sympathetic neurons maintain Ca2+ homeostasis when challenged with high K+ or 8‐(4‐chlorophenylthio)cyclic AMP (CPTcAMP), two survival factors. In the presence of NGF, high K+ (55 mM) caused a stable, 65% reduction in the density of cell soma voltage‐sensitive Ca2+ channels within 2 days. Although resting [Ca2+]i was elevated by 1.6‐fold, this was 50% less than the rise in [Ca2+]i measured before down‐regulation occurred, suggesting that down‐regulation may help prevent the toxic effects of persistently elevated [Ca2+]i. Inhibition of protein synthesis by cycloheximide blocked recovery from down‐regulation. Moreover, treatment with cycloheximide or actinomycin‐D caused a 2‐fold rise in the peak Ca2+ current, suggesting that voltage‐sensitive Ca2+ channel activity may be tonically attenuated during normal growth. In the absence of NGF, neurons survived for several days in high K+ medium with no significant rise in resting [Ca2+]i, although neurites did not grow. Neither Ca2+ channel density nor resting [Ca2+]i were altered in neurons surviving with CPTcAMP. Moreover, CPTcAMP lowered the dependence on extracellular Ca2+. However, the dihydropyridine antagonist nitrendipine blocked both high K+‐ and CPTcAMP‐dependent survival although it had no effect in the presence of NGF. Thus, in the absence of NGF, sympathetic neurons do not require elevation of [Ca2+]i above resting levels to survive with either high K+ or CPTcAMP, but dihydropyridine‐sensitive Ca2+ channel activity may be essential for their survival promoting actions.