bluuebunny/crossref_metadata_2025_split huggingface dataset:
5‐HT1B receptor knockout mice show a compensatory reduction in 5‐HT2C receptor function
Authors: Clifton Peter G. , Lee Michelle D. , Somerville Elizabeth. M. , Kennett Guy A. , Dourish Colin T. 
Published: March 2003

AbstractAlthough null mutant (‘knockout’) mice have provided valuable animal models to complement traditional approaches to psychopharmacology, such animals may also show complex adaptations to the induced mutation. Here we demonstrate that serotonin1B (5‐HT1B) receptor knockout (KO) mice show adaptations in serotonin2C (5‐HT2C) receptor‐mediated functions. They show smaller reductions in food intake and locomotor activity in response to administration of 5‐HT2C receptor agonists that are not accounted for by altered drug disposition. These effects are not mimicked by pretreatment of wildtype (WT) mice with a 5‐HT1B receptor antagonist showing that they result from a longer term adaptation to the loss of 5‐HT1B receptor function and not from a short‐term interaction between 5‐HT1B‐ and 5‐HT2C‐mediated functions. In addition, we show that 5‐HT1B receptor KO mice have a lowered hypothalamic c‐fos response to the administration of 5‐HT2C receptor agonists. These results demonstrate that compensatory adaptations to the constitutive loss of 5‐HT1B receptors may be an important determinant of the altered response of 5‐HT1B KO mice to a variety of pharmacological challenges.
Grasp observation influences speech production
Authors: Gentilucci Maurizio 
Published: March 2003

AbstractSubjects pronounced either the syllable ‘BA’ or ‘GA’ while observing motor acts of hand grasp directed to objects of two sizes (experiment 1). Kinematics of lip aperture and amplitude spectrum of voice were influenced by the observation of the different grasp kinematics depending on the size of the target objects. Specifically, both lip aperture and voice peak amplitude were greater when the observed hand grasp was directed to the large object. Two control experiments ruled out that the different arm velocity when reaching objects varying in size (experiment 2), and overt visual analysis of the target‐object (experiment 3), affected lip movement and voice emission. Results provide behavioural evidence in favour of the hypothesis that the system involved in observation (and preparation) of grasp movements partially shares the cortical areas involved in speech production.
Increase of morphine withdrawal in mice lacking A2a receptors and no changes in CB1/A2a double knockout mice
Authors: Berrendero Fernando , Castañé Anna , Ledent Catherine , Parmentier Marc , Maldonado Rafael , Valverde Olga 
Published: March 2003

AbstractCB1 cannabinoid and A2a adenosine receptors are highly expressed in the central nervous system where they modulate numerous physiological processes including emotional behaviour and the responses of several drugs of abuse. To investigate the contribution of these receptors in emotional‐like responses and opioid dependence we have generated CB1/A2a double deficient mice (\mathrm{CB}^{‐/‐}_{1}/\mathrm{A}^{‐/‐}_{2\mathrm{a}}). The spontaneous locomotor activity was reduced in double knockout as compared to wild‐type animals. Emotional‐like responses of \mathrm{CB}^{‐/‐}_{1}/\mathrm{A}^{‐/‐}_{2\mathrm{a}} mice were investigated using the elevated plus‐maze and the lit‐dark box. Mutant mice exhibited an increased level of anxiety in both behavioural models. The specific involvement of CB1 and A2a receptors in morphine dependence was evaluated by using A2a knockout mice and CB1/A2a double mutant mice. The severity of naloxone‐precipitated morphine withdrawal syndrome was significantly increased in the absence of A2a adenosine receptors whereas no modifications were observed in the double knockout mice. These results suggest that both receptors participate in the control of emotional behaviour and seem to play an opposite role in the expression of opioid physical dependence.
Serial analysis of gene expression predicts structural differences in hippocampus of long attack latency and short attack latency mice
Authors: Feldker Dorine E. M. , Datson Nicole A. , Veenema Alexa H. , Meulmeester Erik , De Kloet E. Ronald , Vreugdenhil Erno 
Published: March 2003

AbstractThe genetically selected long attack latency (LAL) and short attack latency (SAL) mice differ in a wide variety of behavioural traits and display differences in the serotonergic system and the hypothalamus‐pituitary‐adrenocortical (HPA)‐axis. Serial analysis of gene expression (SAGE) was used to generate a hippocampal expression profile of almost 30 000 genes in LAL and SAL mice. Using SAGE, we found differential expression of 191 genes. Among these were genes involved in growth, signal transduction, and cell metabolism. The SAGE study was supported by GeneChip analysis (Affymetrix). Strikingly, both SAGE and GeneChips showed a higher expression of numerous cytoskeleton genes, such as cofilin and several tubulin isotypes in LAL mice. LAL mice also showed a higher expression of several calmodulin‐related genes and genes encoding components of a MAPK cascade, namely raf‐related oncogene and ERK2. The findings were confirmed by in situ hybridization. Our results of differential expression of cytoskeleton and signal transduction genes therefore suggest differential regulation of the raf/ERK pathway that may be related to structural differences in the hippocampus of LAL and SAL mice. As stress‐related disorders, such as depression, are also linked to differential regulation of the HPA‐axis and the serotonergic system and are associated with altered hippocampal morphology, differential regulation of these genes may be involved in the pathogenesis of these diseases.
Protein 4.1B associates with both Caspr/paranodin and Caspr2 at paranodes and juxtaparanodes of myelinated fibres
Authors: Denisenko‐Nehrbass Natalia , Oguievetskaia Ksénia , Goutebroze Laurence , Galvez Thierry , Yamakawa Hisashi , Ohara Osamu , Carnaud Michèle , Girault Jean‐Antoine 
Published: March 2003

AbstractCaspr/paranodin, a neuronal transmembrane glycoprotein, is essential for the structure and function of septate‐like paranodal axoglial junctions at nodes of Ranvier. A closely related protein, Caspr2, is concentrated in juxtaparanodal regions where it associates indirectly with the shaker‐type potassium channels. Although ultrastructural studies indicate that paranodal complexes are linked to the cytoskeleton, the intracellular partners of Caspr/paranodin, as well as those of Caspr2, are poorly characterized. We show that the conserved intracellular juxtamembrane regions (GNP motif) of Caspr/paranodin and Caspr2 bind proteins 4.1R and 4.1B. 4.1B is known to be enriched in paranodal and juxtaparanodal regions. 4.1B immunoreactivity accumulates progressively at paranodes and juxtaparanodes during postnatal development, following the concentration of Caspr/paranodin and Caspr2, respectively, in central and peripheral myelinated axons. These two proteins coimmunoprecipitated with 4.1B in brain homogenates. Our results provide strong evidence for the association of 4.1B with Caspr/paranodin at paranodes and with Caspr2 at juxtaparanodes. We propose that 4.1B anchors these axonal proteins to the actin‐based cytoskeleton in these two regions.
Suprachiasmatic control of melatonin synthesis in rats: inhibitory and stimulatory mechanisms
Authors: Perreau‐Lenz Stéphanie , Kalsbeek Andries , Garidou Marie‐Laure , Wortel Joke , Van Der Vliet Jan , Van Heijningen Caroline , Simonneaux Valérie , Pévet Paul , Buijs Ruud M. 
Published: March 2003

AbstractThe suprachiasmatic nucleus (SCN) controls the circadian rhythm of melatonin synthesis in the mammalian pineal gland by a multisynaptic pathway including, successively, preautonomic neurons of the paraventricular nucleus (PVN), sympathetic preganglionic neurons in the spinal cord and noradrenergic neurons of the superior cervical ganglion (SCG). In order to clarify the role of each of these structures in the generation of the melatonin synthesis rhythm, we first investigated the day‐ and night‐time capacity of the rat pineal gland to produce melatonin after bilateral SCN lesions, PVN lesions or SCG removal, by measurements of arylalkylamine N‐acetyltransferase (AA‐NAT) gene expression and pineal melatonin content. In addition, we followed the endogenous 48 h‐pattern of melatonin secretion in SCN‐lesioned vs. intact rats, by microdialysis in the pineal gland. Corticosterone content was measured in the same dialysates to assess the SCN lesions effectiveness. All treatments completely eliminated the day/night difference in melatonin synthesis. In PVN‐lesioned and ganglionectomised rats, AA‐NAT levels and pineal melatonin content were low (i.e. 12% of night‐time control levels) for both day‐ and night‐time periods. In SCN‐lesioned rats, AA‐NAT levels were intermediate (i.e. 30% of night‐time control levels) and the 48‐h secretion of melatonin presented constant levels not exceeding 20% of night‐time control levels. The present results show that ablation of the SCN not only removes an inhibitory input but also a stimulatory input to the melatonin rhythm generating system. Combination of inhibitory and stimulatory SCN outputs could be of a great interest for the mechanism of adaptation to day‐length (i.e. adaptation to seasons).
Low dose cocaine self‐administration transiently increases but high dose cocaine persistently decreases brain reward function in rats
Authors: Kenny Paul J. , Polis Ilham , Koob George F. , Markou Athina 
Published: March 2003

AbstractThis study investigated the effects of self‐administered cocaine on brain reward function, measured by intracranial self‐stimulation (ICSS) reward thresholds in rats. Self‐administration of 10 and 20 cocaine injections (0.25 mg per injection, equivalent to 4.94 ± 0.23 and 9.88 ± 0.46 mg/kg, self‐administered over 40 ± 6.9 and 99 ± 11.9 min, respectively) lowered reward thresholds 15 min later, indicating a facilitation of rewarding ICSS, but had no effect at 2, 24 or 48 h after administration. Thus, self‐administration of low cocaine doses did not cause persistent changes in brain reward function. Forty cocaine injections (19.64 ± 0.94 mg/kg; self‐administered over 185 ± 10.9 min) also transiently lowered reward thresholds 15 min later, while significant threshold current elevations were observed at 2 and 24 h after administration, indicating persistent withdrawal‐like reward deficits. Finally, 80 cocaine injections (39.53 ± 1.84 mg/kg, self‐administered over 376 ± 19.9 min) significantly elevated thresholds 2 and 48 h after self‐administration, but not at 24 h. Threshold currents also tended to be elevated 15 min after self‐administration. Overall, these data suggest that as the amount of self‐administered cocaine increases the motivation to consume further cocaine may be shifted, from obtaining the rewarding actions of cocaine to avoidance and alleviation of a cocaine‐induced negative affective state.
Age‐dependent cognitive decline in the APP23 model precedes amyloid deposition
Authors: Van Dam Debby , D'Hooge Rudi , Staufenbiel Matthias , Van Ginneken Chris , Van Meir Frans , De Deyn Peter P. 
Published: March 2003

AbstractHeterozygous APP23 mice, expressing human amyloid‐precursor protein with the Swedish double mutation and control littermates, were subjected to behavioral and neuromotor tasks at the age of 6–8 weeks, 3 and 6 months. A hidden‐platform Morris‐type water maze showed an age‐dependent decline of spatial memory capacities in the APP23 model. From the age of 3 months onwards, the APP23 mice displayed major learning and memory deficits as demonstrated by severely impaired learning curves during acquisition and impaired probe trial performance. In addition to the cognitive deficit, APP23 mice displayed disturbed activity patterns. Overnight cage‐activity recording showed hyperactivity in the transgenics for the three age groups tested. However, a short 2‐h recording during dusk phase demonstrated lower activity levels in 6‐month‐old APP23 mice as compared to controls. Moreover, at this age, APP23 mice differed from control littermates in exploration and activity levels in the open‐field paradigm. These findings are reminiscent of disturbances in circadian rhythms and activity observed in Alzheimer patients. Determination of plaque‐associated human amyloid‐β1–42 peptides in brain revealed a fivefold increase in heterozygous APP23 mice at 6 months as compared to younger transgenics. This increase coincided with the first appearance of plaques in hippocampus and neocortex. Spatial memory deficits preceded plaque formation and increase in plaque‐associated amyloid‐β1–42 peptides, but probe trial performance did correlate negatively with soluble amyloid‐β brain concentration in 3‐month‐old APP23 mutants. Detectable plaque formation is not the (only) causal factor contributing to memory defects in the APP23 model.
Olfactory learning modifies the expression of odour‐induced oscillatory responses in the gamma (60–90 Hz) and beta (15–40 Hz) bands in the rat olfactory bulb
Authors: Ravel Nadine , Chabaud Pascal , Martin Claire , Gaveau Valérie , Hugues Etienne , Tallon‐Baudry Catherine , Bertrand Olivier , Gervais Rémi 
Published: March 2003

AbstractThis study addressed the question of the possible functional relevance of two different oscillatory activities, beta and gamma (15–40 and 60–90 Hz, respectively) for perception and memory processes in olfactory areas of mammals. Local field potentials were recorded near relay olfactory bulb neurons while rats performed an olfactory discrimination task. Signals reflected the mass activity from this region and characteristics of oscillatory activities were used as an index of local synchrony. Beta and gamma oscillatory activities were quantified by time‐frequency methods before during and after odour sampling. In rats early in their training, olfactory sampling was associated with a significant decrease in power in the gamma band in parallel with a weak but significant increase in the beta band (centred on 27 Hz). Several days later, in well‐trained rats, the gamma oscillatory depression was significantly enhanced both in duration and amplitude. It appeared within the 500 ms time period preceding odour onset and was further reduced during the odour period. Concurrently the beta oscillatory response (now centred on 24 Hz) during odour sampling was amplified by a twofold factor. The beta band response was modulated according to the chemical nature of the stimuli and rat's behavioural response. This study showed for the first time that odour sampling in behaving animals is associated with a clear shift in the olfactory bulb neuronal activity from a gamma to a beta oscillatory regime. Moreover, the data stress the importance of studying the odour‐induced beta activity and its relation to perception and memory.
The serotonin transporter intronic VNTR enhancer correlated with a predisposition to affective disorders has distinct regulatory elements within the domain based on the primary DNA sequence of the repeat unit
Authors: Lovejoy E. A. , Scott A. C. , Fiskerstrand C. E. , Bubb V. J. , Quinn J. P. 
Published: March 2003

AbstractWe have demonstrated that a variable number tandem repeat domain (VNTR) within intron 2 of the serotonin transporter gene is a transcriptional regulatory domain which is potentially correlated with a predisposition to affective disorders and other behavioural conditions. This correlation based on copy number of the VNTR alone (nine, 10 or 12 copies of 16/17 base‐pair element) has been controversial and not reproduced in all studies. We demonstrate that individual repeat elements within the VNTR domain differ in their enhancer activity in an embryonic stem cell model. This has implications for both the mechanism by which these VNTRs are correlated with the progression of the disease and suggests that clinical analysis should now be extended to correlate sequence variation within the VNTR with the disorder. The latter may resolve some of the conflicting data published to date.
Accumbal dopamine and serotonin in anticipation of the next aggressive episode in rats
Authors: Ferrari P. F. , Van Erp A. M. M. , Tornatzky W. , Miczek K. A. 
Published: March 2003

AbstractAutonomic and limbic neural activities are linked to aggressive behavior, and it is hypothesized that activities in the cardiovascular and monoaminergic systems play a role in preparing for an aggressive challenge. The objective was to learn about the emergence of monoamine activity in nucleus accumbens before an aggressive confrontation that was omitted at the regular time of occurrence, dissociating the motoric from the aminergic activity. Dopamine, serotonin, heart rate and behavioral activity were monitored before, during and after a single 10‐min confrontation in resident male Long‐Evans rats fitted with a microdialysis probe in the n. accumbens and with a telemetry sender (experiment 1). DA, but not 5‐HT efflux, was confirmed to increase in n. accumbens during and after a single aggressive episode. In aggressive males that confronted an opponent daily for 10 days (experiment 2) heart rate rose 1 h before the regularly scheduled encounter relative to control rats, as measured on day 11 in the absence of any aggression. Concurrently, DA levels increased by 60–70% over baseline levels and 5‐HT levels decreased by 30–35% compared to baseline levels. These changes were sustained over 1 h, and contrasted with no significant changes in DA, 5‐HT, heart rate or behavioral activity in control rats. The rise in mesolimbic DA appears to be significant in anticipating the physiological and behavioral demands of an aggressive episode, and the fall in 5‐HT in its termination, dissociated from the actual execution of the behavior.
Neuronal representation of odourants in the olfactory bulb of Xenopus laevis tadpoles
Authors: Czesnik Dirk , Rössler Wolfgang , Kirchner Friedrich , Gennerich Arne , Schild Detlev 
Published: March 2003

AbstractWhen an odourant enters the nose, olfactory receptor neurons (ORNs) convey information about it to the olfactory bulb (OB), where this information is processed and where the first central representations of the odourant are generated. In this paper we show how odourants are represented by ensembles of OB neurons, in particular mitral cells (MCs) which are the output neurons of the OB. We were able to demonstrate for the first time that the intracellular calcium concentrations ([Ca2+]i) in the somata of these neurons undergo specific changes and that different stimuli are represented by different neuronal [Ca2+]i patterns. The similarity of patterns was assessed by cross‐correlation analysis. We further show that noradrenaline (NA), which is reported to be involved in olfactory memory formation and to modulate synaptic transmission at dendrodendritic synapses in the OB, profoundly changes the representation of odourants at the level of MCs.
Imaging of calcineurin activated by long‐term depression‐inducing synaptic inputs in living neurons of rat visual cortex
Authors: Yasuda Hiroki , Higashi Hideyoshi , Kudo Yoshihisa , Inoue Takafumi , Hata Yoshio , Mikoshiba Katsuhiko , Tsumoto Tadaharu 
Published: March 2003

AbstractLong‐term depression (LTD) of synaptic transmission is induced by low‐frequency stimulation (LFS) of afferents lasting for a long time, typically for 10–15 min, in neocortical and hippocampal slices. It is suggested that calcineurin, Ca2+/calmodulin‐dependent protein phosphatase, plays a role in the induction of LTD, based on the results that pharmacological or genetic manipulation of calcineurin activity interfered in its induction. However, questions as to why it takes so long to induce LTD and in which compartment of neurons calcineurin is activated remain unanswered. With a fluorescent indicator for calcineurin activity, we visualized the spatiotemporal pattern of its activation in living neurons in layer II/III of visual cortical slices of rats during the LFS of layer IV that induced LTD of synaptic responses. During LFS, the fluorescence intensity gradually increased with a latency of a few minutes in dendrites and soma of neurons, and remained increased during the whole observation period (10–25 min) after LFS. The onset latency of the increase in the soma was slower than that in the distal dendritic region. The LFS‐induced rise in fluorescence was not observed in neurons which were loaded with inhibitors of calcineurin, indicating that the intensity of fluorescence reflects calcineurin activity. Control stimulation at 0.05 Hz and θ‐burst stimulation did not significantly change the intensity of fluorescence. Only LFS‐type inputs effectively activate calcineurin in postsynaptic neurons in an augmenting manner, and such a time‐consuming activation of calcineurin may be a reason why long‐lasting LFS is necessary for the induction of LTD.
Neurons of the trigeminal main sensory nucleus participate in the generation of rhythmic motor patterns
Authors: Tsuboi A. , Kolta A. , Chen C. C. , Lund J. P. 
Published: March 2003

AbstractThe trigeminal principal sensory nucleus (NVsnpr) contains both trigemino‐thalamic neurons and interneurons projecting to the reticular formation and brainstem motor nuclei. Here we describe the inputs and patterns of firing of NVsnpr neurons during fictive mastication in anaesthetized and paralysed rabbits to determine the role that NVsnpr may play in patterning mastication. Of the 272 neurons recorded in NVsnpr, 107 changed their firing patterns during repetitive stimulation of the left or right sensorimotor cortex to induce fictive mastication. Thirty increased their firing tonically. Seventy‐seven became rhythmically active, but only 31 fired in phase with mastication. The others discharged in bursts at more than twice the frequency of trigeminal motoneurons. Most rhythmic masticatory neurons were concentrated in the dorsal part, and those which fired during the jaw closing phase of the cycle were confined to the anterior pole of the nucleus. Most of these cells had inputs from muscle spindle afferents, whereas most of those firing during jaw opening had inputs from periodontal receptors. Non‐masticatory rhythmical neurons had receptive fields on the lips and face. The majority of rhythmical masticatory units were modulated during fictive mastication evoked by both the left and right cortices and only four changed their phase of firing when switching from one cortex to the other. When coupled with the finding that NVsnpr neurons exhibit spontaneous bursting in vitro[Sandler et al. (1998) Neuroscience, 83, 891], the results described here suggest that neurons of dorsal NVsnpr may form the core of the central pattern generator for mastication.