bluuebunny/crossref_metadata_2025_split huggingface dataset:
Elimination of serotonergic cells induces a marked increase in generation of dopaminergic neurons from mesencephalic precursors
Authors: Rodriguez‐Pallares Jannette , Guerra Maria J. , Labandeira‐Garcia Jose L. 
Published: October 2003

AbstractProduction of dopaminergic (DA) neurons from stem/precursor cells for transplantation in Parkinson's disease has become a major focus of research. However, the inductive signals mediating the production of DA neurons remain poorly understood, and the influence of other cell populations simultaneously generated within the cell aggregates has not been studied. We investigated whether DA phenotype (i.e. tyrosine hydroxylase‐immunoreactive, TH‐ir), serotonergic, floor plate (FP4‐ir), and fibroblast growth factor 8 (FGF‐8)‐ir cells differentiate from proliferating cell aggregates obtained from rat mesencephalic precursors, and we also investigated the effects of serotonergic cells on differentiation of DA cells. We observed FP4‐ir, FGF‐8‐ir, TH‐ir and serotonergic cells within the aggregates. The TH‐ir cells appeared within or in close proximity to a central FP4‐ir core, and then concentrated peripherally forming a cap that surrounded the central FP4‐ir area. The serotonergic cells and fibers formed a cap surrounding that of TH‐ir neurons. Cell aggregates treated with an antibody against FGF‐4 or with the serotonergic toxin 5,7‐dyhydroxytryptamine or the serotonin synthesis inhibitor dl‐p‐chlorophenylalanine showed a marked decrease in the number of 5‐HT‐ir cells (10–20% of controls) and a marked increase in that of TH‐ir neurons (700–900% of controls). The present results show that manipulation of other cell populations in the cell aggregates, particularly the serotonergic population, may be an effective method of increasing the production of DA neurons from stem/precursor cells.
Generation and phenotypic analysis of sigma receptor type I (σ1) knockout mice
Authors: Langa Francina , Codony Xavier , Tovar Victoria , Lavado Alfonso , Giménez Estela , Cozar Patricia , Cantero Marta , Dordal Albert , Hernández Enric , Pérez Raquel , Monroy Xavier , Zamanillo Daniel , Guitart Xavier , Montoliu Lluís 
Published: October 2003

AbstractSigma (σ) sites are a type of nonopiate receptor whose role has been associated with several behaviours, including anxiety, depression, analgesia, learning processes and psychosis. Although there are several known σ receptor types, only the type I receptor (σ1) has been cloned. To uncover thein vivorelevance of σ‐receptors, we have generated knockout mice for σ1. Despite the broad expression pattern found for theσ1‐gene, homozygous mutant mice are viable, fertile and do not display any overt phenotype, compared with their wild‐type litter‐mates, in mixed genetic backgrounds. However, a significant decrease in the hypermotility response has been measured in knockout mice upon challenge with (+)SKF‐10 047, in agreement with the involvement of σ1‐receptors in the induction of psychostimulant actions. The activity of σ2‐receptors seems to be unaffected in σ1‐mutant mice. These knockout mice could contribute to better understand thein vivorole of σ‐receptors.
Cannabinoid receptor and WIN 55 212‐2‐stimulated [35S]‐GTPγS binding in the brain of mu‐, delta‐ and kappa‐opioid receptor knockout mice
Authors: Berrendero Fernando , Mendizábal Victoria , Murtra Patricia , Kieffer Brigitte L. , Maldonado Rafael 
Published: October 2003

AbstractNumerous studies have shown the existence of functional links between the endogenous cannabinoid and opioid systems. However, extensive research is still needed to elucidate the biochemical mechanisms involved in this cannabinoid–opioid interaction. Mice lacking mu‐ (MOR), delta‐ (DOR) and kappa‐ (KOR) opioid receptors have been generated and some specific pharmacological effects induced by cannabinoids have been reported to be modified in these animals. In order to clarify further the possible mechanisms involved in this modification of cannabinoid responses we have now evaluated the expression and functional activity of cannabinoid receptors in different brain structures in these mutant animals. For this purpose, we have performed quantitative receptor autoradiography of CB1 cannabinoid receptors and activation of GTP‐binding proteins by CB1 agonists in the brain of wild‐type and homozygous MOR, DOR and KOR knockout mice. There were no significant differences in the levels of CB1 receptors in the brain of MOR mutant mice. In contrast, the efficacy of CB1 receptor activation by the cannabinoid agonist WIN 55 212‐2 was dramatically reduced in the caudate‐putamen of MOR knockout animals. The density of CB1 receptors as well as the stimulation of GTP‐binding proteins by WIN 55 212‐2 were significantly increased in the substantia nigra of mice deficient in DOR. Finally, there were no major changes in the levels and functional activity of CB1 cannabinoid receptors in any brain region in KOR knockout mice. Taken together, these results indicate that deletion of MOR and DOR causes alterations in cannabinoid receptor levels and functional activity in specific brain structures, which could explain some of the functional interactions observed between these two neuronal systems.
Differential contributions of the basolateral and central nuclei of the amygdala in the negative affective component of chemical somatic and visceral pains in rats
Authors: Tanimoto Sachi , Nakagawa Takayuki , Yamauchi Yosuke , Minami Masabumi , Satoh Masamichi 
Published: October 2003

AbstractPain is a multidimensional conscious experience including sensory and negative affective components. The neural systems of the sensory component of pain have been extensively studied, while those of the negative affective component are less clear. The amygdala is a forebrain structure composed of several distinct nuclei including the basolateral (BLA) and central (CeA) nuclei, and is thought to be a key neural substrate underlying emotional responses. Recently, we reported that intraplantar (i.pl.) injection of formalin as a chemical somatic noxious stimulus increasedc‐fosmRNA expression in the BLA, but not CeA, while intraperitoneal (i.p.) injection of acetic acid as a chemical visceral noxious stimulus induced it highly in the CeA, and hardly in BLA [Nakagawaet al. (2003)Neurosci. Lett., 344, 197–200]. In this study, we examined the effects of discrete bilateral excitotoxic lesions of the BLA or CeA on the sensory and negative affective components of the two types of pain in Sprague–Dawley rats. In the place‐conditioning paradigm, both i.pl. formalin and i.p. acetic acid produced conditioned place aversion. The i.pl. formalin‐induced conditioned place aversion was abolished by the lesion of the BLA or CeA, while the i.p. acetic acid‐induced conditioned place aversion was abolished by the CeA‐, but not BLA‐lesion. On the other hand, the BLA‐ or CeA‐lesion failed to reduce the i.pl. formalin‐ and i.p. acetic acid‐produced nociceptive behaviours. Taken together, these results suggest that activation of distinct amygdaloid nuclei could differentially contribute to chemical somatic and visceral noxious stimuli‐induced negative affective, but not sensory components of pains.
Haploinsufficiency in trkB and/or trkC neurotrophin receptors causes structural alterations in the aged hippocampus and amygdala
Authors: Von Bohlen und Halbach Oliver , Minichiello Liliana , Unsicker Klaus 
Published: October 2003

AbstractNeurotrophins and their cognate trk receptors regulate key events, most notably survival and differentiation of specific neuron populations, during the development of the nervous system. Their functions in the adult and aged CNS are far less well understood. We have analysed mice aged 21–23 months with haploinsufficiencies of the trkB and/or trkC genes with regard to morphological alterations in the hippocampus and amygdala. Neuronal densities and total numbers of neurons in the dentate gyrus were significantly decreased in trkB+/−, trkC+/−, and trkB+/−/C+/− mutants. In the hippocampal area CA2/3, neuronal density and the total number of neurons were only reduced in double‐heterozygous mice. Within the amygdala, neuronal densities were not altered. The lateral, basolateral and basomedial nuclei of the amygdala, as well as the dentate gyrus and area CA3, revealed significant increases in the densities of degenerated axonal fragments; the most pronounced changes were found in the double‐heterozygous mice. Thus, partial impairment in trkB and/or trkC receptor expression caused region‐specific neuron losses in the hippocampus and increased axonal fragmentation in both hippocampus and amygdala, which may result from degeneration of both intrinsic and extrinsic fibre systems. Together, these data indicate that endogenous ligands to the trkB and trkC receptors are essential to maintain neuronal integrity in the aged hippocampus and amygdala.
Hippocampal N‐acetyl aspartate levels do not mirror neuronal cell densities in creatine‐supplemented epileptic rats
Authors: Vielhaber Stefan , Kudin Alexei P. , Kudina Tatiana A. , Stiller Detlef , Scheich Henning , Schoenfeld Ariel , Feistner Helmut , Heinze Hans‐Jochen , Elger Christian E. , Kunz Wolfram S. 
Published: October 2003

AbstractFor neuroprotective therapy of neurodegenerative diseases creatine treatment has gained special interest because creatine has been shown to cross the blood–brain barrier, accumulate in the human brain in vivo and cause delayed neuronal cell death in a large number of animal models. Here, we used the pilocarpine model of temporal lobe epilepsy to determine whether creatine administration is able to attenuate the epilepsy‐associated decrease in hippocampal N‐acetyl aspartate (NAA) concentrations, impairment of mitochondrial function and neuronal cell loss. In vivo1H‐NMR spectroscopy showed, in epileptic rats after creatine administration, higher hippocampal NAA concentrations, suggesting improved neuronal survival. However, in vitro observation of hippocampal slices from creatine‐treated epileptic rats revealed a more pronounced loss of pyramidal neurons and decrease in activity of mitochondrial enzymes in hippocampal subfields. This indicates that NAA concentrations measured by in vivo1H‐NMR spectroscopy reflect alterations of metabolism rather than neuronal cell densities. Our data indicate an adverse effect of creatine on neuronal survival under conditions of enhanced neuronal activity.
Development of Ca2+‐channel and BK‐channel expression in embryos and larvae of Xenopus laevis
Authors: Jiménez‐González Cristina , McLaren Gerald J. , Dale Nicholas 
Published: October 2003

AbstractThe patterns and density of channels expressed in neurons critically determine their electrical properties. We have examined developmental regulation of Ca2+‐channel expression during the maturation of the spinal motor circuits in Xenopus as it develops from an embryo to a larva. In embryonic neurons ≈ 60% of the current is carried by N‐type channels, 8% by l‐type channels and the remainder by an unidentified channel. As the embryo matures, ω‐agatoxin‐sensitive P/Q channels are gradually expressed and replace the unidentified HVA channel such that at stage 42 ≈ 25% of the current is carried by P/Q channels. We have used fluorescent labelling of selective channel toxins to directly observe the distribution of P/Q, N and BK channels. The P/Q channel distribution was most prevalent on the cell surface proximal to the areas of the soma where processes emerge. Both N and BK channels were distributed throughout the soma but still exhibited concentration around the areas adjacent to the emergence of processes from the soma. The patterns of fluorescence labelling during development mirrored the development of the respective ionic currents. Both N and P/Q channels contribute roughly equally to activation of the BK current, suggesting that overlap in the distribution of the N, P/Q and BK channels is important in their functional interdependence. The newly expressed P/Q channels play a role in spike initiation and repetitive firing in larval spinal neurons and contribute to burst generation during swimming in the larva.
Attention and working memory: a dynamical model of neuronal activity in the prefrontal cortex
Authors: Deco Gustavo , Rolls Edmund T. 
Published: October 2003

AbstractCognitive behaviour requires complex context‐dependent mapping between sensory stimuli and actions. The same stimulus can lead to different behaviours depending on the situation, or the same behaviour may be elicited by different cueing stimuli. Neurons in the primate prefrontal cortex show task‐specific firing activity during working memory delay periods. These neurons provide a neural substrate for mapping stimulus and response in a flexible, context‐ or rule‐dependent, fashion. We describe here an integrate‐and‐fire network model to explain and investigate the different types of working‐memory‐related neuronal activity observed. The model contains different populations (or pools) of neurons (as found neurophysiologically) in attractor networks which respond in the delay period to the stimulus object, the stimulus position (‘sensory pools’), to combinations of the stimulus sensory properties (e.g. the object identity or object location) and the response (‘intermediate pools’), and to the response required (left or right) (‘premotor pools’). The pools are arranged hierarchically, are linked by associative synaptic connections, and have global inhibition through inhibitory interneurons to implement competition. It is shown that a biasing attentional input to define the current rule applied to the intermediate pools enables the system to select the correct response in what is a biased competition model of attention. The integrate‐and‐fire model not only produces realistic spiking dynamicals very similar to the neuronal data but also shows how dopamine could weaken and shorten the persistent neuronal activity in the delay period; and allows us to predict more response errors when dopamine is elevated because there is less different activity in the different pools of competing neurons, resulting in more conflict.
Self‐face processing in a callosotomy patient
Authors: Keenan Julian Paul , Wheeler Mark , Platek Steven M. , Lardi Gina , Lassonde Maryse 
Published: October 2003

AbstractSelf‐face recognition is reserved for humans, apes and possibly dolphins and is thought to be a marker of self‐awareness. Previous data have indicated that self‐face recognition may be mediated via frontal right hemisphere circuits within the brain. Testing patient M.L., who underwent a total callosotomy, we found that when searching for the self‐face in a series of morphs (composite facial images made up of his own and a famous face in inversely varying percentages) the patient made (i) more true‐positive and (ii) fewer false‐positive responses when responding with the right hemisphere (i.e. indicating with the left hand). There was no hand difference when searching for familiar faces. These data imply a right hemisphere processing advantage for self‐faces.
Lesions of the mammillothalamic tract impair the acquisition of spatial but not nonspatial contextual conditional discriminations
Authors: Vann Seralynne D. , Honey R. C. , Aggleton John P. 
Published: October 2003

AbstractThis study examined the influence of selective mammillothalamic tract lesions in rats on the acquisition of two kinds of contextual conditional discrimination: one involving two contexts (A and B) that differed in their visuo‐spatial properties and another involving two contexts (C and D) that differed in temperature. In contexts A (and C) presentations of a tone were paired with food whereas presentations of a clicker were not; and in contexts B (and D) presentations of the clicker were paired with food whereas those of the tone were not. Mammillothalamic tract lesions disrupted initial acquisition of the conditional discrimination involving visual contexts (A and B), but not the formally equivalent discrimination involving thermal contexts (C and D). These results provide support for the suggestion that mammillothalamic tract lesions disrupt visuo‐spatial encoding.
Sex hormone‐dependent desensitization of 5‐HT1A autoreceptors in knockout mice deficient in the 5‐HT transporter
Authors: Bouali Saoussen , Evrard Alexis , Chastanet Michel , Lesch Klaus‐Peter , Hamon Michel , Adrien Joëlle 
Published: October 2003

AbstractThe serotonin transporter (5‐HTT) is the target of most antidepressant drugs, whose therapeutic action is related to their facilitatory influence on 5‐HT neurotransmission. In this study, we investigated the functional adaptive properties of 5‐HT1A autoreceptors, which regulate serotonergic neuronal firing, in knockout mice deficient in 5‐HTT. Neurons of the dorsal raphe nucleus (DRN) were recorded extracellularly under chloral hydrate anaesthesia in male and female knockout 5‐HTT mice and their wild‐type counterparts. The inhibitory response of DRN neurons to intravenous injection of the 5‐HT1A agonist 8‐OH‐DPAT was dramatically reduced in knockout 5‐HTT compared with wild‐type mice, especially in females. Changes in 8‐OH‐DPAT‐induced hypothermia and autoradiographic labelling of 5‐HT1A sites in the DRN confirmed a greater level of desensitization/down‐regulation of 5‐HT1A autoreceptors in female than in male knockout 5‐HTT mice. After gonadectomy, the functional status of 5‐HT1A autoreceptors was unchanged in wild‐type mice, whereas in knockout 5‐HTT, castrated males exhibited a down‐regulation, and ovariectomized females an up‐regulation of these receptors, as shown by electrophysiological recording and autoradiographic labelling in the DRN, as well as by changes in 8‐OH‐DPAT‐induced hypothermia. Finally, in gonadectomized knockout 5‐HTT mice, treatment with testosterone or estradiol restored the DRN neuronal firing sensitivity to 8‐OH‐DPAT back to sham control level in males or females, respectively. These data indicate that sexual hormones participate in the mechanisms responsible for the desensitization of 5‐HT1A autoreceptors in knockout 5‐HTT mice. The differential effects of testosterone and estradiol on 5‐HT1A‐mediated control of 5‐HT neurotransmission might be related to the well‐established gender differences in the vulnerability to depression.
Augmentation of induced visual gamma activity by increased task complexity
Authors: Posada Andres , Hugues Etienne , Franck Nicolas , Vianin Pascal , Kilner James 
Published: October 2003

AbstractRecently the study of induced gamma band oscillations has focused on their modulation by top‐down processes, mainly attention. Numerous studies have observed an increase in induced gamma band energy with increases in covert selective attention and visual perception. The current study investigated the modulation of visually induced gamma band oscillations by top‐down processes associated with task complexity. Fourteen human subjects performed a reaction time task under two experimental conditions that differed in task complexity. In one, subjects simply had to press one of four buttons that corresponded to a colour stimulus shown to the subject. In the second, the stimulus response mapping was altered by the implementation of a rule, thus increasing task complexity. Cortical electrical activity was recorded using a 65 electrode whole scalp electroencephalographic (EEG) net. The EEG activity was analysed using Morlet wavelets to produce time–frequency maps. Although induced gamma band activity was observed in both conditions, there was significantly greater energy during the rule‐operation condition at approximately 276 ms after the appearance of the stimulus. This increase was localized to electrodes overlying the right‐central parietal scalp. The results of this study show that top‐down processes modulate the level of induced gamma band activity. We discuss these findings in terms of the role of gamma oscillations in the construction of a sensory representation useful for a correct motor response.
Rapid and long‐term alterations of hippocampal GABAB receptors in a mouse model of temporal lobe epilepsy
Authors: Straessle Andrea , Loup Fabienne , Arabadzisz Dimitrula , Ohning Gordon V. , Fritschy Jean‐Marc 
Published: October 2003

AbstractAlterations of γ‐aminobutyric acid (GABA)B receptor expression have been reported in human temporal lobe epilepsy (TLE). Here, changes in regional and cellular expression of the GABAB receptor subunits R1 (GBR1) and R2 (GBR2) were investigated in a mouse model that replicates major functional and histopathological features of TLE. Adult mice received a single, unilateral injection of kainic acid (KA) into the dorsal hippocampus, and GABAB receptor immunoreactivity was analysed between 1 day and 3 months thereafter. In control mice, GBR1 and GBR2 were distributed uniformly across the dendritic layers of CA1–CA3 and dentate gyrus. In addition, some interneurons were labelled selectively for GBR1. At 1 day post‐KA, staining for both GBR1 and GBR2 was profoundly reduced in CA1, CA3c and the hilus, and no interneurons were visible anymore. At later stages, the loss of GABAB receptors persisted in CA1 and CA3, whereas staining increased gradually in dentate gyrus granule cells, which become dispersed in this model. Most strikingly, a subpopulation of strongly labelled interneurons reappeared, mainly in the hilus and CA3 starting at 1 week post‐KA. In double‐staining experiments, these cells were selectively labelled for neuropeptide Y. The number of GBR1‐positive interneurons also increased contralaterally in the hilus. The rapid KA‐induced loss of GABAB receptors might contribute to epileptogenesis because of a reduction in both presynaptic control of transmitter release and postsynaptic inhibition. In turn, the long‐term increase in GABAB receptors in granule cells and specific subtypes of interneurons may represent a compensatory response to recurrent seizures.
Distribution and pharmacology of alanine–serine–cysteine transporter 1 (asc‐1) in rodent brain
Authors: Helboe Lone , Egebjerg Jan , Møller Morten , Thomsen Christian 
Published: October 2003

AbstractA polyclonal antibody against the Na+‐independent alanine–serine–cysteine transporter 1 (asc‐1) was raised and the specificity of the antibody verified by Western blots performed on membranes prepared from HEK293 cells transiently transfected with the cloned murine asc‐1. The antibody was then used to localize the transporter in the brain of two rodent species by using immunohistochemistry at the light and electron microscopical level. asc‐1‐immunoreactivity (asc‐1‐ir) was widely distributed throughout the mouse and rat brain. Areas with high levels of asc‐1‐ir included hypothalamus, the medial septal area, globus pallidus, entopeduncular nucleus, cingulate and retrosplenial cortices. Moderate asc‐1‐ir was observed in several areas including layers III and V of the neocortex, thalamus, nucleus accumbens, caudate putamen, bed nucleus of stria terminalis, all amygdaloid nuclei, hippocampus (CA1–CA3 and hilus of the dentate gyrus), as well as several brainstem nuclei. asc‐1‐ir was observed as punctuate staining consistent with varicosities matching neuronal cell bodies and dendritic fields. At the ultrastructural level, asc‐1‐ir was mainly confined to presynaptic terminals. Immunostaining in either glial cell bodies or perivascular sites was not observed and white matter was completely devoid of asc‐1‐ir. Furthermore, the pharmacology of the Na+‐independent uptake site for [3H]d‐serine in rat brain synaptosomal P2 fractions was compared with the substrate specificity of the cloned human asc‐1 transporter and a high degree of correlation was demonstrated. We conclude that asc‐1‐ir is widespread in the brain and limited to neuronal structures and that asc‐1 may contribute to synaptic clearance of d‐serine in brain.