bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pierre Dionis and the Franco−British dialogue in surgery
Authors: Simpson Donald 
Published: May 2003

Pierre Dionis (1643?−1718), though not himself a very innovative surgeon, has been acclaimed as the author of a surgical textbook that opened a new era in which French surgical teaching dominated Europe. This dominance is reflected in the Gordon Craig Library, which contains four copies of the book by Dionis in English translation, as well as a number of other books by influential French 18th century surgical writers, notably Henri François Le Dran and François Quesnay. It is significant that many of these writers benefited from government patronage in various forms. Dionis himself began his career as demonstrator in anatomy and surgery at the Jardin du Roi, in his time the premier teaching institution in those sciences. He later became a court surgeon. During the course of the 18th century, French surgery gained ascendancy over French academic medicine and also on the inter­national stage. English surgery, likewise, made great progress. There was a very productive dialogue between medical scientists and teachers in both countries, assisted by textbooks in translation. The French Revolution demolished the medical and surgical institutions established under the old regime, but French surgery emerged from the rubble to play a great part in the birth of modern clinical medicine
Intrinsic light responses of retinal ganglion cells projecting to the circadian system
Authors: Warren Erin J. , Allen Charles N. , Brown R. Lane , Robinson David W. 
Published: May 2003

AbstractIn mammals, light entrainment of the circadian clock, located in the suprachiasmatic nuclei (SCN), requires retinal input. Traditional rod and cone photoreceptors, however, are not required. Instead, the SCN‐projecting retinal ganglion cells (RGCs) function as autonomous photoreceptors and exhibit light responses independent of rod‐ and cone‐driven input. Using whole‐cell patch‐clamp recording techniques, we have investigated the morphological and electrophysiological properties of this unique class of RGCs. Although SCN‐projecting RGCs resemble Type III cells in form, they display strikingly different physiological properties from these neurons. First, in response to the injection of a sustained depolarizing current, SCN‐projecting cells fired in a transient fashion, in contrast to most RGCs which fired robust trains of action potentials. Second, in response to light, SCN‐projecting RGCs exhibited an intensity‐dependent transient depolarization in the absence of rod and cone input. This depolarization reached a peak within 5 s and generated increased spiking activity before decaying to a plateau. Voltage‐clamp recordings were used to characterize the light‐activated conductance which generated this depolarization. In response to varying light intensities, SCN‐projecting RGCs exhibited a graded transient inward current which peaked within 5 s and decayed to a plateau. The voltage dependence of the light‐activated current was obtained by subtracting currents elicited by a voltage ramp before and during illumination. The light‐activated current displayed both inward and outward rectification and was largely unaffected by substitution of extracellular Na+ with choline. In both respects, the intrinsic light‐activated current observed in SCN‐projecting RGCs resembles currents carried by ion channels of the transient receptor potential (trp) family, which are known to mediate the light response of invertebrate photoreceptors.
Ontogenetic development of cannabinoid receptor expression and signal transduction functionality in the human brain
Authors: Mato Susana , Del Olmo Elena , Pazos Angel 
Published: May 2003

AbstractPrevious evidence suggests that the endogenous cannabinoid system emerges relatively early during brain development in the rat. However, the pre‐ and postnatal pattern of appearance of CB1 cannabinoid receptors in humans has not been analysed in detail. Furthermore, there is a complete lack of information about the functional ability of these proteins to activate signal transduction mechanisms during human development. In the present study we have explored CB1 receptor expression throughout the different areas of the developing human brain by [3H]CP55 940 autoradiography. We have also assessed CB1 functional coupling to G proteins during brain development by agonist‐stimulated [35S]GTPγS autoradiography in the same cases. Our results indicate a significant density of cannabinoid receptors at 19 weeks' gestation in the same areas that contain these receptors in the adult human brain. Autoradiographic levels of CB1 receptors in these structures seem to increase progressively from early prenatal stages to adulthood. Interestingly, high densities of cannabinoid receptors have also been detected during prenatal development in fibre‐enriched areas that are practically devoid of them in the adult brain. In parallel with these data, we have found that brain cannabinoid receptors are functionally coupled to signal transduction mechanisms from early prenatal stages. This early pattern of expression of functionally active cannabinoid receptors, along with the transient and atypical localization of these proteins in white matter areas during the prenatal stages, suggest an specific role of the endocannabinoid system in the events related to human neural development.
Neurokinin 1 receptor and relative abundance of the short and long isoforms in the human brain
Authors: Caberlotto Laura , Hurd Yasmin L. , Murdock Paul , Wahlin Jean Philippe , Melotto Sergio , Corsi Mauro , Carletti Renzo 
Published: May 2003

AbstractSubstance P exerts its various biochemical effects mainly via interactions through neurokinin‐1 receptors (NK1). Recently, the NK1 receptor has attracted considerable interest for its possible role in a variety of psychiatric disorders including depression and anxiety. However, little is known regarding the anatomical distribution of NK1 in the human central nervous system (CNS). Riboprobe in situ hybridization, quantitative PCR and in vitro autoradiography were performed. Highest NK1 mRNA levels were localized in the locus coeruleus and ventral striatum, while moderate hybridization signals were observed in the cerebral cortex (most abundant in the visual cortex), hippocampus and different amygdaloid nuclei. Very low levels of the NK1 mRNA were detected in the cerebellum and thalamus. In view of the existence of a long and short isoform of the NK1 receptor, it was of interest to assess whether there was a differential distribution of the two splice variants in the human CNS and peripheral tissues. A quantitative TaqMan PCR analysis showed that the long NK1 isoform was the most prevalent throughout the human brain, while in peripheral tissues the truncated form was the most represented. 3H‐Substance P autoradiography revealed a good correlation between receptor binding sites and NK1 mRNA expression throughout the brain, with the highest levels of binding in the locus coeruleus. These results provide the anatomical evidence that the NK1 receptors have a strong association with neuronal systems relevant to mood regulation and stress in the human brain, but do not suggest a region‐specific role of the two isoforms in the CNS.
Interhemispheric visuo‐motor integration in humans: the effect of redundant targets
Authors: Iacoboni Marco , Zaidel Eran 
Published: May 2003

AbstractWe used event‐related functional magnetic resonance imaging (fMRI) to investigate the functional locus of response facilitation during parallel visuo‐motor processing. In a simple reaction‐time task, subjects typically respond faster to two copies of the same stimulus than to a single copy. This facilitation, called the redundant‐target effect, can occur at three functional levels: perceptual, ‘cognitive’ or motor. Normal right handers were studied while performing a simple reaction‐time task to unilateral (left or right) and bilateral light flashes. Subjects were instructed to respond with their right index finger. Reaction times were faster to bilateral light flashes than to unilateral ones, even right flashes. Greater fMRI signal for bilateral stimuli compared to unilateral ones was observed in the left precentral and postcentral gyrus, and in the right precentral gyrus. A greater fMRI signal for bilateral and for unilateral left stimuli, compared to unilateral right stimuli, was observed in an area of the right intraparietal sulcus. These results support the hypothesis that the functional locus of response facilitation during parallel visuo‐motor processing is premotor.
Blockade of nociceptin/orphanin FQ–NOP receptor signalling produces antidepressant‐like effects: pharmacological and genetic evidences from the mouse forced swimming test
Authors: Gavioli E. C. , Marzola G. , Guerrini R. , Bertorelli R. , Zucchini S. , De Lima T. C. M , Rae G. A. , Salvadori S. , Regoli D. , Calo G. 
Published: May 2003

AbstractNociceptin/orphanin FQ (N/OFQ), the endogenous ligand of the NOP receptor, regulates several central functions such as pain transmission, learning and memory, fear and anxiety and feeding and locomotor activity. It has been recently reported that NOP receptor antagonists induce antidepressant‐like effects in the mouse forced swimming test (FST), i.e. reduce immobility time. This assay was used in the present study for further investigating the involvement of the NOP receptor in depression states. In male Swiss mice, intracerebroventricular injection (i.c.v) of the novel NOP receptor antagonist, UFP‐101 (1–10 nmol) dose‐dependently reduced the immobility time (control 192 ± 14 s, UFP‐101 91 ± 15 s). The effect of 3 or 10 nmol UFP‐101 was fully or partially reversed, respectively, by the coadministration of 1 nmol N/OFQ, which was inactive per se. NOP receptor knockout mice showed a reduced immobility time compared with their wild‐type littermates (wild‐type 215 ± 10 s, knockout 143 ± 12 s). Moreover, i.c.v. injected UFP‐101 (10 nmol) significantly reduced immobility time in wild‐type mice but not in NOP receptor knockout animals. In conclusion, these results, obtained using a combined pharmacological and genetic approach, indicate that blockade of the N/OFQ‐NOP receptor signalling in the brain produces antidepressant‐like effects in the mouse FST. These findings support the NOP receptor as a candidate target for the development of innovative antidepressant drugs.
Enzymatic removal of chondroitin sulphates abolishes the age‐related axon order in the optic tract of mouse embryos
Authors: Leung Kim‐Mei , Taylor Jeremy S. H. , Chan Sun‐On 
Published: May 2003

AbstractRetinal axons undergo an age‐related reorganization at the junction of the chiasm and the optic tract. We have investigated the effects of removal of chondroitin sulphate on this order change in mouse embryos aged embryonic day 14, when most axons are growing in the optic tract. Enzymatic removal of chondroitin sulphate but not keratan sulphate in brain slice preparations of the retinofugal pathway abolished the accumulation of phalloidin‐positive growth cones in the subpial region of the optic tract. The loss of chronotopicity was further demonstrated by anterograde filling of single retinal axons, which showed a dispersion of growth cones from subpial to the whole depth of the tract. The enzyme treatment neither produced detectable changes in growth cone morphology and growth dynamic of retinal neurites nor affected the radial glial processes in the tract, indicating a specific effect of removal of chondroitin sulphate from the pathway to the axon order in the tract. Although chondroitin sulphate was also found at the midline of the chiasm, growth cone distribution across the depth of fibre layer at the midline was not affected by the enzyme treatment. These results suggest a mechanism in which retinal axons undergo changes in response to chondroitin sulphate at the chiasm–tract junction, but not at the midline, that produce a chronotopic fibre rearrangement in the mouse retinofugal pathway.
γ‐Frequency fluctuations of the membrane potential and response selectivity in visual cortical neurons
Authors: Volgushev Maxim , Pernberg Joachim , Eysel Ulf T. 
Published: May 2003

AbstractFluctuations at frequencies of 25–70 Hz is an inherent property of cortical activity. These rapid, γ‐range fluctuations are apparent in the local field potentials, in spiking of cells and cell groups, and in the membrane potential of neurons. To investigate stimulus dependence of the γ‐frequency fluctuations of the membrane potential, we have recorded intracellularly responses of cells in cat visual cortex to presentation of moving gratings. We found γ‐range fluctuations of the membrane potential in both simple and complex cells. The strength of the γ‐frequency fluctuations correlated with the stimulus optimality. Furthermore, the amplitude of the γ‐frequency fluctuations correlated with the phase of stimulus‐imposed slow changes of the membrane potential. The combination of these features makes cortical neurons capable of encoding the slow changes in the visual world in a kind of amplitude modulation of the high frequency fluctuations. This assures reliable transformation of the membrane potential changes into spike responses without compromising the temporal resolution of visual information encoding in the low frequency range.
Learning deficits and dysfunctional synaptic plasticity induced by aggregated amyloid deposits in the dentate gyrus are rescued by chronic treatment with indomethacin
Authors: Stéphan Aline , Laroche Serge , Davis Sabrina 
Published: May 2003

AbstractThe amyloid pathology in Alzheimer's disease is accompanied by a chronic inflammatory response characterized by gliosis and activated microglial cells surrounding senile plaques. Epidemiological studies have shown nonsteroidal anti‐inflammatory drug treatment reduces the risk of Alzheimer's disease. We have previously shown that injection of a combination of Aβ40 and Aβ43 in the dentate gyrus of the rat induces aggregated amyloid deposits and inflammation associated with dysfunctional synaptic plasticity and learning deficits. Here we characterize the effectiveness of nonsteroidal anti‐inflammatory treatment in this model and show that this treatment restores the working memory deficit and decremental long‐term potentiation in the dentate gyrus. Importantly, we observe no qualitative difference in the presence of aggregated material but a substantial reduction in microglial‐induced inflammation, suggesting that mature aggregated plaques may not be directly responsible for the deficits but may trigger an inflammatory response which has a detrimental effect on synaptic function and memory.
Modulation of GABAergic transmission by endogenous glutamate in the rat supraoptic nucleus
Authors: Piet Richard , Bonhomme Renée , Theodosis Dionysia T. , Poulain Dominique A. , Oliet Stéphane H. R. 
Published: May 2003

AbstractThe presence of group III metabotropic glutamate receptors on GABAergic terminals in the supraoptic nucleus suggests that the level of glutamate in the extracellular space may regulate synaptic strength at inhibitory synapses. To test this hypothesis we examined the consequences of increasing ambient glutamate on GABA‐mediated synaptic activity in supraoptic neurons. The concentration of the excitatory amino acid in the extracellular space was increased pharmacologically by blocking glutamate transporters. Inhibition of the astrocyte‐specific GLT‐1 glutamate transporter led to a reversible decrease in evoked inhibitory postsynaptic current amplitude. This modulation had a presynaptic origin as revealed by analysis of paired‐pulse ratio and miniature inhibitory currents. Furthermore, blocking group III metabotropic glutamate receptors with the specific antagonist MAP4 prevented the depression of GABAergic transmission induced by glutamate transporter blockade. Thus, presynaptic metabotropic glutamate receptors located on inhibitory terminals in the supraoptic nucleus appear to sense changes in ambient glutamate and modify GABA release accordingly. However, it seems that such changes need to reach a certain magnitude because the discrete deficit in glutamate clearance which occurs in the supraoptic nucleus of lactating rats is not sufficient to modulate GABA‐mediated transmission. These results suggest that ambient glutamate contributes to the modulation of synaptic efficacy not only at glutamatergic synapses but also at inhibitory GABAergic synapses.
Effect of sleep and sleep deprivation on serotonergic neurotransmission in the hippocampus: a combined in vivo microdialysis/EEG study in rats
Authors: Peñalva Rosana G. , Lancel Marike , Flachskamm Cornelia , Reul Johannes M. H. M. , Holsboer Florian , Linthorst Astrid C. E. 
Published: May 2003

AbstractBrainstem serotonergic neurotransmission is implicated in sleep regulation. However, the role of serotonin (5‐HT) in forebrain regions in sleep–wake mechanisms is still unclear. Here, we have investigated, using a combined in vivo microdialysis/electroencephalogram method, the relationship between hippocampal 5‐HT levels and sleep–wake behaviour in the rat. A clear‐cut relationship was found between hippocampal 5‐HT levels and vigilance state. The highest levels of 5‐HT were observed during wakefulness, whereas a progressive decrease of 5‐HT going from nonrapid eye movement sleep to rapid eye movement sleep was found. Sleep deprivation (SD) causes a transient enhancement of mood in depressed patients. Given the putative role of 5‐HT in the aetiology of depression and the therapeutical efficacy of selective serotonin reuptake inhibitors in this illness, we also studied hippocampal 5‐HT during 4 h of SD and during the subsequent recovery period. During the whole SD period, 5‐HT levels were elevated substantially when compared to 5‐HT levels during basal wakefulness. However, no changes in 5‐HT levels and the relationship between hippocampal 5‐HT and vigilance state were found during the subsequent recovery period. As SD is a potentially stressful experience and glucocorticoids are involved in the regulation of serotonergic neurotransmission and sleep, we investigated the effects of SD on free corticosterone levels. SD caused a marked rise in free corticosterone levels. However, the effects of SD on 5‐HT seem not to be mediated by this hormone, because adrenalectomy did not affect the rise in hippocampal 5‐HT during SD. We hypothesize that the elevated hippocampal 5‐HT levels during SD may participate in the transient mood enhancing properties of forced wakefulness observed in depressed patients.
Evidence for a function‐specific mutation in the neurotoxin, parabutoxin 3
Authors: Huys Isabelle , Tytgat Jan 
Published: May 2003

AbstractParabutoxin 3 (PBTx3), a short‐chain α‐K+ neurotoxin from the scorpion, Parabuthus transvaalicus, is a 37‐residue polypeptide cross‐linked by three disulphide bridges. The affinity towards Kv1 channels is very weak (Kd ≈ 79 µm for Kv1.1 channels), or moderate (Kd ≈ 500 nm for Kv1.2 and Kv1.3 channels). In an effort to generate a more potent K+ channel blocker, we recombinantly produced a mutant PBTx3 by the introduction of an aromatic amino acid, fenylalanine in close proximity of the crucial lysine 26 residue, to create a functional diad similar to subfamily three α‐K+ toxins. The mutant was tested for his ability to block Kv1.1, Kv1.2 and Kv1.3 channels in Xenopus laevis oocytes: a hundred‐fold higher affinity towards Kv1.1 channels and a fivefold increase in affinity towards Kv1.3 channels was observed, when compared to the wild‐type toxin. The effect on Kv1.2 channels was similar to the wild‐type toxin, indicating a specific interaction site for the mutated residue onto the different Kv‐type channels.
The effects of ibotenic hippocampal lesions on discriminative fear conditioning to context in mice: impairment or facilitation depending on the associative value of a phasic explicit cue
Authors: Desmedt Aline , Marighetto Aline , Garcia René , Jaffard Robert 
Published: May 2003

AbstractTo what extent the hippocampus is required for contextual conditioning remains a matter of debate. The present experiments examined the effects of ibotenate hippocampal lesions on discriminative fear conditioning to context in mice using measures of freezing in two conditioning paradigms. In both paradigms animals received foot shock as the unconditional stimulus (US) when placed in the (conditioning) context and no foot‐shock when placed in the other (neutral) context. In both contexts, animals were presented with a tone as the conditioned stimulus (CS). In the conditioning context there was either no interval (delay condition) or a 30‐s interval (trace condition) between tone CS end and shock US onset. These two paradigms were used because theory predicts that in the trace condition animals would learn more about contextual cues as predictors, or not, of shock US occurrence than in the delay condition. In agreement with this, we observed that sham‐operated mice learned the context discrimination faster in the trace than in the delay condition. Lesions of the hippocampus significantly retarded, but did not prevent, the acquisition of the context discrimination in the trace condition. In contrast, lesions produced an opposite (facilitatory) effect in the delay condition, which was mainly observed during tone CS presentation. The data suggest that mice used two distinct competing strategies in solving this discrimination task: (i) a strategy relying on the processing of background contextual stimuli allowing direct establishment of context–US associations of different strengths, and (ii) a conditional cue (tone)‐based strategy. Hence, hippocampal lesions may impair the use of the former strategy while exacerbating (unmasking) the use of the latter.
Melanopsin retinal ganglion cells and the maintenance of circadian and pupillary responses to light in aged rodless/coneless (rd/rd cl) mice
Authors: Semo Ma'ayan , Peirson Stuart , Lupi Daniela , Lucas Robert J. , Jeffery Glen , Foster Russell G. 
Published: May 2003

AbstractMelanopsin‐expressing ganglion cells have been proposed as the photoreceptors mediating non‐rod, non‐cone ocular responses to light. Here we use the aged (approximately 2 years) rodless and coneless (rd/rd cl) mouse to assess the impact of progressive inner retinal cell loss on melanopsin expression, circadian entrainment and pupillary constriction. Aged rd/rd cl mice show substantial transneuronal retinal degeneration leaving only the ganglion cell layer and little of the inner nuclear layer. Despite this loss, quantitative reverse transcriptase‐polymerase chain reaction showed normal levels of melanopsin expression, and immunocytochemistry demonstrated both the presence and normal cellular appearance of these cells. Furthermore, the optic nerves of the two genotypes (rd/rd cl and +/+) were not obviously different in animals older than 2 years. However, this massive level of retinal degeneration left both pupillary and circadian responses to light intact, even in rd/rd cl mice older than 2 years. Our data provide the first positive correlation between the persistence of melanopsin‐expressing cells and the maintenance of both circadian and pupillary responses to light in the absence of rods and cones. These findings, together with recent studies on melanopsin knockout mice, are consistent with the hypothesis that melanopsin‐expressing ganglion cells are photosensitive and mediate a range of irradiance‐detection tasks.