bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fos imaging reveals ageing‐related changes in hippocampal response to radial maze discrimination testing in mice
Authors: Touzani Khalid , Marighetto Aline , Jaffard Robert 
Published: March 2003

AbstractA two‐stage radial arm maze (RAM) task has been designed recently to demonstrate a specific age‐related memory deficit in mice. It highlights the contrast between normal and deficient memory expression in a spatial discrimination problem depending on how to‐be discriminated arms were presented to the animal. This specific deficit has been interpreted as a preferential loss in a relational/declarative form of memory, thereby implying an underlying hippocampal dysfunction. To test this hypothesis, neuronal activation measured by Fos immunostaining was compared in aged (21–23 months) and adult (4–6 months) mice trained in the aforementioned task and killed after a retention session consisting in age‐insensitive probe trials, performed 6 days later (6‐day RAM). Two comparison conditions were included: (i) repeated locomotor training on a treadmill (TM); (ii) the same RAM training, except for the use of a longer (30 days instead of six) retention interval (30‐day RAM). Although all RAM groups displayed similar levels of performance at the end of the experiment, immediately before the mice were killed, significant between‐group differences in brain activation were observed. In adult mice, 6‐day RAM testing was associated with greater septal and hippocampal (CA1, CA3, DG) Fos expression than the TM condition. Lengthening the retention interval from 6 days to 30 days resulted in a significant decrease in RAM testing‐induced Fos expression in most of the septo‐hippocampal regions. With respect to adult mice, aged mice displayed reduced Fos expression (except for DG) and a lack of interrelationships between levels of Fos produced in each of the SH regions, in the 6‐day RAM testing condition. Conversely, there was no effect of ageing on Fos expression associated with either TM training or 30‐day RAM testing. These results are interpreted as reflecting age‐ (or time‐) related alterations in recruiting of brain structures that underlie a relational/declarative form of memory expression.
Electrophysiological evidence for convergence of inputs from the medial prefrontal cortex and lateral habenula on single neurons in the dorsal raphe nucleus
Authors: Varga V. , Kocsis B. , Sharp T. 
Published: March 2003

AbstractNeuronal projections to the dorsal raphe nucleus (DRN) from the medial prefontal cortex (mPFC) and lateral habenula nucleus (LHb) provide the two key routes by which information processed by mood regulatory, cortico‐limbic‐striatal circuits input into the 5‐HT system. These two projections may converge as it appears that both activate local GABAergic neurons to inhibit 5‐HT neurons in the DRN. Here we have tested this hypothesis by measuring the effect of stimulation of the mPFC and LHb on the activity of 5‐HT and non‐5‐HT, putative γ‐amino butyric acid (GABA) neurons in the DRN using extracellular recordings in anaesthetized rats. A total of 119 5‐HT neurons (regular, slow firing, broad spike width) and 21 non‐5‐HT, putative GABA neurons (fast‐firing, narrow spike width) were tested. Electrical stimulation of the mPFC or LHb caused a poststimulus inhibition (30 ms latency) of 101/119 5‐HT neurons, of which 61 (60%) were inhibited by both the mPFC and LHb. Electrical stimulation of the mPFC or LHb also caused a short latency (12–20 ms) poststimulus facilitation of 10/21 non‐5‐HT neurons, of which 5 (50%) were activated by both the mPFC and LHb. These data indicate that a significant number of 5‐HT neurons and non‐5‐HT neurons in the DRN are influenced by both the mPFC and LHb. Moreover, the data are compatible with the hypothesis and that there is a convergence of mPFC and LHb inputs on local circuit GABAergic neurons in the DRN which in turn inhibit the activity of 5‐HT neurons.
Endogenous and exogenous dopamine presynaptically inhibits glutamatergic reticulospinal transmission via an action of D2‐receptors on N‐type Ca2+ channels
Authors: Svensson Erik , Wikström Martin A. , Hill Russell H. , Grillner Sten 
Published: March 2003

AbstractIn this study, the effects of exogenously applied and endogenously released dopamine (DA), a powerful modulator of the lamprey locomotor network, are examined on excitatory glutamatergic synaptic transmission between reticulospinal axons and spinal neurons. Bath application of DA (1–50 µm) reduced the amplitude of monosynaptic reticulospinal‐evoked glutamatergic excitatory postsynaptic potentials (EPSPs). The effect of DA was blocked by the D2‐receptor antagonist eticlopride, and mimicked by the selective D2‐receptor agonist 2,10,11 trihydroxy‐N‐propyl‐noraporphine hydrobromide (TNPA). Bath application of the DA reuptake blocker bupropion, which increases the extracellular level of dopamine, also reduced the monosynaptic EPSP amplitude. This effect was also blocked by the D2‐receptor antagonist eticlopride. To investigate if the action of DA was exerted at the presynaptic level, the reticulospinal axon action potentials were prolonged by administering K+ channel antagonists while blocking l‐type Ca2+ channels. A remaining Ca2+ component, mainly dependent on N and P/Q channels, was depressed by DA. When DA (25–50 µm) was applied in the presence of ω‐conotoxin GVIA, a toxin specific for N‐type Ca2+ channels, it failed to affect the monosynaptic EPSP amplitude. DA did not affect the response to extracellularly ejected d‐glutamate, the postsynaptic membrane potential, or the electrical component of the EPSPs. DA thus acts at the presynaptic level to modulate reticulospinal transmission.
The effects of nitric oxide on magnocellular neurons could involve multiple indirect cyclic GMP‐dependent pathways
Authors: Vacher C. M. , Hardin‐Pouzet H. , Steinbusch H. W. M. , Calas A. , De Vente J. 
Published: March 2003

AbstractNitric oxide (NO) is known to regulate the release of arginine‐vasopressin (AVP) and oxytocin (OT) by the paraventricular nucleus (PVN) and the supraoptic nucleus (SON). The aim of the current study was to identify in these nuclei the NO‐producing neurons and the NO‐receptive cells in mice. The determination of NO‐synthesizing neurons was performed by double immunohistochemistry for the neuronal form of NO synthase (NOS), and AVP or OT. Besides, we visualized the NO‐receptive cells by detecting cyclic GMP (cGMP), the major second messenger for NO, by immunohistochemistry on hypothalamus slices. Neuronal NOS was exclusively colocalized with OT in the PVN and the SON, suggesting that NO is mainly synthesized by oxytocinergic neurons in mice. By contrast, cGMP was not observed in magnocellular neurons, but in GABA‐, tyrosine hydroxylase‐ and glutamate‐positive fibers, as well as in GFAP‐stained cells. The cGMP‐immunostaining was abolished by incubating brain slices with a NOS inhibitor (L‐NAME). Consequently, we provide the first evidence that NO could regulate the release of AVP and OT indirectly by modulating the activity of the main afferents to magnocellular neurons rather than by acting directly on magnocellular neurons. Moreover, both the NADPH‐diaphorase activity and the mean intensity of cGMP‐immunofluorescence were increased in monoamine oxidase A knock‐out mice (Tg8) compared to control mice (C3H) in both nuclei. This suggests that monoamines could enhance the production of NO, contributing by this way to the fine regulation of AVP and OT release and synthesis.
A radialization factor in normal cortical plate restores disorganized radial glia and disrupted migration in a model of cortical dysplasia
Authors: Hasling Thomas A. , Gierdalski Marcin , Jablonska Beata , Juliano Sharon L. 
Published: March 2003

AbstractTreatment of pregnant ferrets on embryonic day 24 (E24) with the antimitotic methylazoxy methanol (MAM) leads to a specific constellation of effects in newborn kits, which include a very thin and poorly laminated neocortex, disruption of radial glial cell morphology with early differentiation into astrocytes, and abnormal positioning of Cajal–Retzius cells. We suggest that MAM treatment on E24 results in this model of cortical dysplasia by eliminating a population of cells that produce a factor capable of maintaining radial glia in their normal morphology. The abnormal radial glia, either alone or in combination with other abnormal features, are likely to prevent proper migration into the cortical plate. To test the possibility that normal cortex can provide the missing substance that influences radial glia, slices of E24 MAM‐treated cortex were removed at postnatal day 0 (P0) and cultured adjacent to explants of P0 normal cortical plate. By labelling a small number of cells with injections of fluorescent dextrans into the cultured slices, we found that abnormal radial glia in MAM treated slices cocultured adjacent to normal cortical plate were restored toward normal, in comparison to E24 MAM treated slices cultured alone and in other control conditions. We also found that abnormally positioned Cajal–Retzius cells move into the marginal zone and that neurons are able to migrate into the cortical plate more effectively in the coculture condition. These data indicate that normal cortical plate of ferrets contains a factor causing radial glia to maintain their elongated morphology; the improved position of radial glia encourages repositioning of Cajal–Retzius cells and improved neuronal migration into the cortical plate.
Time course of striatal ΔFosB‐like immunoreactivity and prodynorphin mRNA levels after discontinuation of chronic dopaminomimetic treatment
Authors: Andersson M. , Westin J. E. , Cenci M. A. 
Published: March 2003

AbstractΔFosB‐like proteins are particularly stable transcription factors that accumulate in the brain in response to chronic perturbations. In this study we have compared the time‐course of striatal FosB/ΔFosB‐like immunoreactivity and prodynorphin mRNA expression after discontinuation of chronic cocaine treatment to intact rats and chronic L‐DOPA treatment to unilaterally 6‐hydroxydopamine (6‐OHDA) lesioned rats. The animals were killed between 3 h and 16 days after the last drug injection. In both treatment paradigms, the drug‐induced FosB/ΔFosB immunoreactivity remained significantly elevated in the caudate putamen even at the longest withdrawal period examined. The concomitant upregulation of prodynorphin mRNA, a target of ΔFosB, paralleled the time‐course of ΔFosB‐like immunoreactivity in the 6‐OHDA‐lesion/L‐DOPA model, but was more transient in animals treated with cocaine. These results suggest that ΔFosB‐like proteins have exceptional in vivo stability. In the dopamine‐denervated striatum, these proteins may exert sustained effects on the expression of their target genes long after discontinuation of L‐DOPA pharmacotherapy.
Intrathecally applied flurbiprofen produces an endocannabinoid‐dependent antinociception in the rat formalin test
Authors: Ates Mehmet , Hamza May , Seidel Kay , Kotalla Carolin E. , Ledent Catherine , Gühring Hans 
Published: March 2003

AbstractIt is generally accepted that the phospholipase‐A2‐cyclooxygenase‐prostanoids‐cascade mediates spinal sensitization and hyperalgesia. However, some observations are not in line with this hypothesis. The aim of the present work was to investigate whether different components of this cascade exhibit nociceptive or antinociceptive effects in the rat formalin test. Intrathecal (i.th.) injection of prostaglandin E2 (PGE2) induced a dose‐dependent antinociceptive effect on the formalin‐induced nociception. Furthermore, thimerosal, which inhibits the reacylation of arachidonic acid thereby enhancing arachidonic acid levels, had an antinociceptive effect rather than the expected pronociceptive effect when given i.th. While the phospholipase A2 inhibitor methyl arachidonyl fluorophosphonate (MAFP; i.th.) had a significant antinociceptive effect, its analogue palmitoyl trifluoromethyl ketone (PTFMK; i.th.) had no significant effect on the formalin‐induced nociception. However, MAFP, but not PTFMK, showed a cannabinoid CB1 agonistic effect as shown by the inhibition of electrically evoked contractions of the vas deferens isolated from CB1 wild‐type mice but not of that from CB1 knockout mice. The antinociceptive effect of MAFP was completely reversed by the CB1 receptor antagonist AM‐251 (i.th.), thus attributing such effect to its CB1 agonistic effect. Moreover, the antinociceptive effect of the cyclooxygenase inhibitor, flurbiprofen (i.th.) was reversed by the co‐administration of AM‐251, but not by PGE2. Finally. the combination of phenylmethylsulfonyl fluoride (PMSF; intraperitoneal), which inhibits the degradation of anandamide through the inhibition of fatty acid amidohydrolase, with thimerosal (i.th.) produced a profound CB1‐dependent antinociception. The present results show that endocannabinoids play a major role in mediating flurbiprofen‐induced antinociception at the spinal level.
Differential galanin receptor‐1 and galanin expression by 5‐HT neurons in dorsal raphé nucleus of rat and mouse: evidence for species‐dependent modulation of serotonin transmission
Authors: Larm Jari A. , Shen Pei‐Juan , Gundlach Andrew L. 
Published: March 2003

AbstractGalanin and galanin receptors are widely expressed by neurons in rat brain that either synthesize/release and/or are responsive to, classical transmitters such as γ‐aminobutyric acid, acetylcholine, noradrenaline, histamine, dopamine and serotonin (5‐hydroxytryptamine, 5‐HT). The dorsal raphé nucleus (DRN) contains ≈ 50% of the 5‐HT neurons in the rat brain and a high percentage of these cells coexpress galanin and are responsive to exogenous galanin in vitro. However, the precise identity of the galanin receptor(s) present on these 5‐HT neurons has not been previously established. Thus, the current study used a polyclonal antibody for the galanin receptor‐1 (GalR1) to examine the possible expression of this receptor within the DRN of the rat and for comparative purposes also in the mouse. In the rat, intense GalR1‐immunoreactivity (IR) was detected in a substantial population of 5‐HT‐immunoreactive neurons in the DRN, with prominent receptor immunostaining associated with soma and proximal dendrites. GalR1‐IR was also observed in many cells within the adjacent median raphé nucleus. In mouse DRN, neurons exhibited similar levels and distribution of 5‐HT‐IR to that in the rat, but GalR1‐IR was undetectable. Consistent with this, galanin and GalR1 mRNA were also undetectable in mouse DRN by in situ hybridization histochemistry, despite the detection of GalR1 mRNA (and GalR1‐IR) in adjacent cells in the periaqueductal grey and other midbrain areas. 5‐HT neuron activity in the DRN is primarily regulated via 5‐HT1A autoreceptors, via inhibition of adenylate cyclase and activation of inward‐rectifying K+ channels. Notably, the GalR1 receptor subtype signals via identical mechanisms and our findings establish that galanin modulates 5‐HT neuron activity in the DRN of the rat via GalR1 (auto)receptors. However, these studies also identify important species differences in the relationship between midbrain galanin and 5‐HT systems, which should prompt further investigations in relation to comparative human neurochemistry and which have implications for studies of animal models of relevant neurological conditions such as stress, anxiety and depression.
Differential routing of coexisting neuropeptides in vasopressin neurons
Authors: Landry Marc , Vila‐Porcile Evelyne , Hökfelt Tomas , Calas André 
Published: March 2003

AbstractThe functional implications of intraneuronal coexistence of different neuropeptides depend on their respective targeting to release sites. In the rat hypothalamic magnocellular neurons, we investigated a possible differential routing of the coexpressed galanin and vasopressin. The respective location of proteins and messengers was assessed with double immunogold and in situ hybridization combining confocal and electron microscope analysis. The various populations of labelled granules were quantitatively compared in three subcellular compartments: perikarya, local processes and posthypophyseal nerve endings. Three subpopulations of granules were detected in all three compartments, but their respective amount showed significant differences. Galanin alone was immunolocalized in some secretory granules, vasopressin alone in others, and both peptides in a third subpopulation of granules. The major part of the granules containing vasopressin, either alone or in association with galanin, is found in neurohypophyseal nerve endings. In contrast, galanin single‐labelled granules represent the most abundant population in dendritic processes, while double‐labelled granules are more numerous in perikarya. This indicates a preferential distribution of the two peptides in the different compartments of magnocellular neurons. Furthermore, galanin and vasopressin messenger RNAs were detected at different domains of the endoplasmic reticulum, suggesting that translation might also occur at different locations, thus leading to partial segregation of galanin and vasopressin cargoes between two populations of secretory granules. The present study provides, for the first time in mammals, evidence suggesting that galanin and vasopressin are only partly copackaged and undergo a preferential targeting toward dendrites or neurohypophysis, suggesting different functions, autocrine/paracrine and endocrine, respectively.
Rat strain differences in peripheral and central serotonin transporter protein expression and function
Authors: Fernandez Francesca , Sarre Sophie , Launay Jean‐Marie , Aguerre Sylvie , Guyonnet‐Dupérat Véronique , Moisan Marie‐Pierre , Ebinger Guy , Michotte Yvette , Mormède Pierre , Chaouloff Francis 
Published: March 2003

AbstractFemale Fischer 344 (F344) rats have been shown to display increased serotonin transporter (5‐HTT) gene expression in the dorsal raphe, compared to female Lewis (LEW) rats. Herein, we explored, by means of synaptosomal preparations and in vivo microdialysis, whether central, but also peripheral, 5‐HTT protein expression/function differ between strains. Midbrain and hippocampal [3H]paroxetine binding at the 5‐HTT and hippocampal [3H]serotonin (5‐HT) reuptake were increased in male and female F344 rats, compared to their LEW counterparts, these strain differences being observed both in rats of commercial origin and in homebred rats. Moreover, in homebred rats, it was found that these strain differences extended to blood platelet 5‐HTT protein expression and function. Saturation studies of midbrain and hippocampal [3H]paroxetine binding at the 5‐HTT, and hippocampal and blood platelet [3H]5‐HT reuptake, also revealed significant strain differences in Bmax and Vmax values. Although F344 and LEW rats differ in the activity of the hypothalamo‐pituitary‐adrenal (HPA) axis, manipulations of that axis revealed that the strain differences in hippocampal [3H]paroxetine binding at 5‐HTTs and [3H]5‐HT reuptake were not accounted for by corticosteroids. Hippocampal extracellular 5‐HT levels were reduced in F344 rats, compared to LEW rats, with the relative, but not the absolute, increase in extracellular 5‐HT elicited by the local administration of citalopram being larger in F344 rats. Because the aforementioned strain differences did not lie in the coding sequences of the 5‐HTT gene, our results open the promising hypothesis that F344 and LEW strains model functional polymorphisms in the promoter region of the human 5‐HTT gene.
Cognitive control processes during an anticipated switch of task
Authors: Wylie G. R. , Javitt D. C. , Foxe J. J. 
Published: March 2003

AbstractFor successful negotiation of our environment, humans must be readily able to switch from one task to another. This ability relies on ‘executive control’ processes and despite extensive efforts to detail the nature of these processes, there is little consensus as to how the brain achieves this critical function. Behavioural studies show that as subjects are given more time to prepare to switch task, performance improves; yet even with the longest preparation intervals, there remains an ineradicable performance cost on switch trials. As such, some elements of the switching process must wait until the stimulus to be acted upon has actually been presented. Here, using the methods of high‐density mapping of brain potentials, we show that early visual processes are substantially different on switch trials than on later trials. Our data show that while there is clearly a degree of preparatory processing that occurs prior to a predictable switch of task, some elements of switching are only achieved after the switch stimulus has been presented. Our findings are discussed in the context of a new model of executive control processes that suggests that preparing to switch task may not be a separate (control) processper se, but rather, the beginning of a competition between the potentially relevant tasks, a competition that is ultimately resolved during the switch trial.
Impairments in visual discrimination after perirhinal cortex lesions: testing ‘declarative’ vs. ‘perceptual‐mnemonic’ views of perirhinal cortex function
Authors: Bussey Timothy J. , Saksida Lisa M. , Murray Elisabeth A. 
Published: March 2003

AbstractTwo experiments tested the predictions of ‘declarative’ vs. ‘perceptual‐mnemonic’ views of perirhinal cortex function. The former view predicts that perirhinal cortex lesions should impair rapidly learned, but not more slowly learned, visual discriminations, whereas the latter view predicts that impairments should be related not to speed of learning but to perceptual factors. It was found that monkeys with perirhinal cortex lesions were impaired in the acquisition and performance of slowly learned, perceptually difficult greyscale picture discriminations, but were not impaired in the acquisition of rapidly learned, perceptually easier discriminations. In addition, these same monkeys were not impaired in the acquisition or performance of difficult colour or size discriminations, indicating that the observed pattern of impairments was not due to ceiling effects or difficultyper se. These findings, taken together, are consistent with the ‘perceptual‐mnemonic’ view that the perirhinal cortex is involved in both perception and memory, but are not consistent with the ‘declarative’ view that the perirhinal cortex is important exclusively for declarative memory, having little or no role in perception. Moreover, the results are consistent with the more specific proposal that the perirhinal cortex contributes to the solution of complex visual discriminations with a high degree of ‘feature ambiguity’, a property of visual discrimination problems that can emerge when features of an object are rewarded when part of one object, but not when part of another. These and other recent findings suggest the need for a revision of prevailing views regarding the neural organization of perception and memory.