bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intravenous cocaine induced‐activity and behavioural sensitization in norepinephrine‐, but not dopamine‐transporter knockout mice
Authors: Mead Andy N. , Rocha Beatriz A. , Donovan David M. , Katz Jonathan L. 
Published: March 2003

AbstractPreviously, it was reported that both norepinephrine transporter (NET) and dopamine transporter (DAT) knockout (KO) mice were sensitive to the reinforcing effects of cocaine. However, assessing the locomotor‐stimulant effects of cocaine in these subjects has proven difficult due to significant differences in their baseline activity compared to wild‐type controls. The present studies were designed to clarify the role of NET and DAT in the stimulant effects of acute and repeated cocaine utilizing these knockout mice, and thereby assess the role of these substrates in the locomotor stimulant effects of cocaine. Mice were habituated to the test environment for sufficient time to ensure equal baselines at the time of cocaine administration. Mice then received cocaine (3–25 mg/kg) intravenously according to a within‐session cumulative dose–response design. Cocaine dosing was repeated at 48‐h intervals for four sessions to assess behavioural sensitization. NET‐KO mice exhibited a reduced response to acute cocaine administration compared to wild‐type (WT) controls. However, comparable sensitization developed in NET‐KO and WT mice. The DAT‐KO and DAT‐heterozygote (HT) mice displayed no locomotor activation following either acute or repeated cocaine administration. These data suggest a role for the NET in the acute response to cocaine, but no involvement in sensitization to cocaine. In contrast, DAT appears to be necessary for both the acute locomotor response to cocaine and the subsequent development of sensitization. In addition to existing data concerning the reinforcing effects of cocaine in DAT‐KO mice, these data suggest a dissociation between the reinforcing and locomotor stimulant effects of cocaine.
Genes controlling hypothalamic development and sexual differentiation*
Authors: Tobet Stuart A. 
Published: March 2003

AbstractSteroid hormones dramatically influence the development of numerous sites in the nervous system. Basic mechanisms in neural development provide foci for understanding how factors related to sex can alter the ontogeny of these regions. Sex differences in neurogenesis, cell migration, cell differentiation, cell death, and synaptogenesis are being addressed. Any and all of these events serve as likely targets for genetic or gonadal steroid‐dependent mechanisms throughout development. Although the majority of sexually dimorphic characteristics in brain have been described in older animals, many hormonal mechanisms that determine sexually differentiated brain characteristics occur during critical perinatal periods. Genes suggested to contribute to the development of specific hypothalamic nuclear groups have rarely been examined in the context of sex. The identification of sex differences in the expression of some of these genes may suggest early and likely transient molecular events that set the stage for later amplification by hormone actions. Sex differences in the positioning of cells in the developing hypothalamus further suggest that cell migration may be one key target for early gene actions that impact long‐term susceptibility to brain sexual differentiation.
Tissue plasminogen activator is required for corticostriatal long‐term potentiation
Authors: Centonze Diego , Napolitano Maddalena , Saulle Emilia , Gubellini Paolo , Picconi Barbara , Martorana Alessandro , Pisani Antonio , Gulino Alberto , Bernardi Giorgio , Calabresi Paolo 
Published: March 2003

AbstractSeveral experimental data indicate that tissue plasminogen activator (tPA) is involved in memory formation and synaptic plasticity in different brain areas. In the attempt to highlight the role of this serine protease in striatal neuron activity, mice lacking tPA have been used for electrophysiological, immunohistochemical and Western blot experiments. Disruption of tPA gene prevented corticostriatal long‐term potentiation, an NMDA‐dependent form of synaptic plasticity requiring the stimulation of both dopamine and acetylcholine receptors. Spontaneous and evoked glutamatergic transmission was intact in the striatum of tPA‐deficient mice, as was the nigrostriatal dopamine innervation and the expression of dopamine D1 receptors. Conversely, the sensitivity of striatal cholinergic interneurons to dopamine D1 receptor stimulation was lost in these mutants, suggesting that tPA facilitates long‐term potentiation (LTP) induction in the striatum by favouring the D1 receptor‐mediated excitation of acetylcholine‐producing interneurons. The demonstration that tPA ablation interferes with the induction of corticostriatal LTP and with the dopamine receptor‐mediated control of cholinergic interneurons might help to explain the altered striatum‐dependent learning deficits observed in tPA‐deficient mice and provides new insights into the molecular mechanisms underlying synaptic plasticity in the striatum.
Serotonin differentially modulates the electrical properties of different subsets of taste receptor cells in bullfrog
Authors: Imendra Kotapola G. , Miyamoto Takenori , Okada Yukio , Toda Kazuo 
Published: March 2003

AbstractSerotonin (5‐hydroxytryptamin, 5‐HT) is localized in taste bud cells of vertebrates. Effects of the external application of 5‐HT on the membrane currents of frog taste receptor cells (TRCs) were investigated using patch‐clamp technique in whole‐cell configuration. The 5‐HT (0.1–1 µm) and 5‐HT1A receptor agonist (+/–)‐8‐OH‐2‐(D1‐n‐propyl‐amino)tetralin (8‐OH‐DPAT) (1–20 µm) inhibited both voltage‐gated sodium current (INa) and voltage‐gated potassium current (IK) in 50% of TRCs, but potentiated IK without any significant effect on INa in another subset of 18% of TRCs. Voltage‐gated currents in the residual TRCs were not affected by 5‐HT or 8‐OH‐DPAT. External application of 10 µm forskolin and 300 µm 8‐cpt cAMP [8‐(4‐chlorophenylthio)adenosine 3′:5′‐cyclic monophosphate] mimicked the inhibitory effect of 5‐HT and 8‐OH‐DPAT on IK and INa while internal dialysis with 50 µm protein kinase A inhibitor prevented the 5‐HT‐mediated inhibitory effects on IK and INa in TRCs. Internal dialysis of TRCs with high Ca2+‐pipette solution (1 µm) increased the IK in 58% of TRCs. The 5‐HT reversibly increased the [Ca2+]i in 17% of TRCs when measured by Ca2+‐imaging using a Ca2+‐sensitive dye (fura‐2 AM). These results suggest that 5‐HT differentially modulates the voltage‐gated membrane currents in different subsets of TRCs.
Differential and long‐lasting alterations of high‐voltage activated calcium currents in CA1 and dentate granule neurons after status epilepticus
Authors: Gorter Jan A. , Borgdorff Aren J. , Van Vliet Erwin A. , Da Silva Fernando H. Lopes , Wadman Wytse J. 
Published: March 2003

AbstractThe effects on high‐voltage activated (HVA) calcium currents were examined in hippocampal CA1 cells and dentate gyrus (DG) granule neurons, 2 days (short‐term; ST) and 2–3 months (long‐term; LT) after electrically induced, limbic electrographic and behavioural seizures in rats. Whole‐cell voltage‐clamp recordings in dissociated CA1 neurons of LT rats showed a decrease in the sustained HVA calcium current amplitude and a faster inactivation of the current both in rats that had experienced a status epilepticus (post‐SE rats) and those in which the stimulation did not lead to SE (non‐SE rats). In CA1 neurons of LT–SE rats this resulted in a reduced Ca2+ entry through the HVA channels. Perforated‐patch voltage‐clamp recordings in dissociated DG granule neurons of LT–SE rats showed an increased sustained HVA current amplitude compared to controls and non‐SE rats, leading to an increased Ca2+ entry via HVA calcium channels. Two days after SE, we observed an increased Ca2+ entry for a defined depolarization, although the change in HVA current amplitude and inactivation rate did not reach significance. We also observed a decrease in calbindin‐D28k staining in DG post‐SE neurons, but this change was not associated with a change in HVA current inactivation. The opposite changes in neuronal Ca2+ entry through HVA channels in CA1 vs. DG cells depended strongly on whether rats had experienced SE and later spontaneous seizure activity. These changes are likely to contribute to regionally different effects on local network excitability.
A divergent gene family encoding candidate olfactory receptors of the moth Heliothis virescens
Authors: Krieger Jürgen , Raming Klaus , Dewer Youssef M. E. , Bette Stefanie , Conzelmann Sidonie , Breer Heinz 
Published: March 2003

AbstractThe antennae of moths have been an invaluable model for studying the principles of odour perception. In spite of the enormous progress in understanding olfaction on the molecular level, for the moth one of the key elements in olfactory signalling, the odourant receptors, are still elusive. We have assessed a genome database of a heliothine moth (Heliothis virescens, Noctuidae) and employed exon‐specific probes to screen an antennal cDNA library of this species. Analysis of isolated cDNA‐clones led to the discovery of a divergent gene family encoding putative seven‐transmembrane domain proteins. The notion that they may encode candidate olfactory receptors of the moth, was supported by a tissue‐specific expression; several of the subtypes were exclusively expressed in antennae. By means of double‐labelling in situ hybridization studies it was demonstrated that the receptors are indeed expressed in antennal sensory neurons; moreover, each receptor subtype appears to be expressed in a distinct population of sensory cells. The results strongly suggest that the newly discovered gene family indeed encodes olfactory receptors of moth.
Influences of the corticotropic axis and sympathetic activity on neurochemical consequences of 3,4‐methylenedioxymethamphetamine (MDMA) administration in Fischer 344 rats
Authors: Fernandez Francesca , Aguerre Sylvie , Mormède Pierre , Chaouloff Francis 
Published: March 2003

AbstractThe respective influences of the corticotropic axis and sympathetic activity on 3,4‐methylenedioxymethamphetamine (MDMA, ecstasy) immediate effects on body temperature and long‐term neurotoxicity, as assessed by decreases in hippocampal and striatal [3H]5‐hydroxytryptamine ([3H]5‐HT) reuptake, [3H]paroxetine binding at 5‐HT transporters (5‐HTT), and 5‐HT and 5‐hydroxyindoleacetic acid (5‐HIAA) levels, were examined in Fischer 344 rats. On each of the two injections of MDMA (5 or 10 mg/kg s.c. once a day for 2 consecutive days) body temperature rapidly increased in a dose‐dependent manner. Six days after the last injection of 10 mg/kg MDMA, [3H]5‐HT reuptake, [3H]paroxetine binding and 5‐HT and 5‐HIAA levels were decreased in the hippocampus and, to a lower extent, in striatum. Prior adrenalectomy (1 week beforehand), which weakened the immediate hyperthermic effect of MDMA, prevented the long‐term MDMA‐elicited reduction in hippocampal and striatal [3H]paroxetine binding. Supplementation of adrenalectomised Fischer 344 rats with corticosterone almost reinstated the immediate hyperthermic effect of MDMA and restored MDMA‐elicited reduction in hippocampal and striatal [3H]paroxetine binding. In a final set of experiments, Fischer 344 rats were pretreated (30 min before each of the two injections of 10 mg/kg MDMA) with the ganglionic blocker chlorisondamine (2.5 mg/kg). This pretreatment markedly reduced the amplitudes of the immediate hyperthermia and long‐term declines in hippocampal [3H]5‐HT reuptake and [3H]paroxetine binding at 5‐HTT, and in hippocampal and striatal 5‐HT and 5‐HIAA levels. These results suggest that sympathetic activity (possibly through its control of body temperature), but not corticotropic activity, plays a key role in MDMA‐elicited neurotoxicity in Fischer 344 rats.
Degeneration of pontine mossy fibres during cerebellar development in weaver mutant mice
Authors: Ozaki Miwako , Hashikawa Tsutomu , Ikeda Kazutaka , Miyakawa Yukie , Ichikawa Tomio , Ishihara Yoshihiro , Kumanishi Toshiro , Yano Ryoji 
Published: March 2003

AbstractIn weaver mutant mice, substitution of an amino acid residue in the pore region of GIRK2, a subtype of the G‐protein‐coupled inwardly rectifying K+ channel, changes the properties of the homomeric channel to produce a lethal depolarized state in cerebellar granule cells and dopaminergic neurons in substantia nigra. Degeneration of these types of neurons causes strong ataxia and Parkinsonian phenomena in the mutant mice, respectively. On the other hand, the mutant gene is also expressed in various other brain regions, in which the mutant may have effects on neuronal survival. Among these regions, we focused on the pontine nuclei, the origin of the pontocerebellar mossy fibres, projecting mainly into the central region of the cerebellar cortex. The results of histological analysis showed that by P9 the number of neurons in the nuclei was reduced in the mutant to about one half and by P18 to one third of those in the wild type, whereas until P7 the number were about the same in wild‐type and weaver mutant mice. Three‐dimensional reconstruction of the nuclei showed a marked reduction in volume and shape of the mutant nuclei, correlating well with the decrease in neuronal number. In addition, DiI (a lipophilic tracer dye) tracing experiments revealed retraction of pontocerebellar mossy fibres from the cerebellar cortex after P5. From these results, we conclude that projecting neurons in the pontine nuclei, as well as cerebellar granule cells and dopaminergic neurons in substantia nigra, strongly degenerate in weaver mutant mice, resulting in elimination of pontocerebellar mossy fibres during cerebellar development.
Spontaneous network activity of cerebellar granule neurons: impairment by in vivo chronic cannabinoid administration
Authors: Ghozland Sandy , Aguado Fernando , Espinosa‐Parrilla Juan F. , Soriano Eduardo , Maldonado Rafael 
Published: March 2003

AbstractSynchronized activity of neuronal networks has been proposed to be essential for cerebellar function. To examine the occurrence and organization of spontaneous neuronal activity in the cerebellum in vivo, we imaged mouse cerebellar slices loaded with the intracellular Ca2+ concentration indicator, fura‐2. Recordings were then analysed statistically to identify correlated network activity. Ca2+ imaging revealed consistent spontaneous correlated network activity of granule cells (GC), which often occurred in clusters of coactivated GC. The number of spontaneously active GC, their activation frequency and correlation, were controlled by glutamate and GABA ionotropic receptors. These findings indicate that distinctive patterns of correlated activity between GC networks may be relevant for cerebellar circuit function. Cannabinoid antagonist‐precipitated Δ9‐tetrahydrocannabinol (THC) withdrawal impaired motor coordination. Given that the cerebellum has been suggested recently to be a main substrate for cannabinoid withdrawal, we used imaging of spontaneous network activity to examine whether GC, which contain CB1 cannabinoid receptors, respond to chronic THC treatment and withdrawal. Acute administration of THC had no effect on patterns of spontaneous GC network activity. In contrast, chronic THC administration severely impaired GC activity and network coordination. Incubation of cerebellar slices, from chronically THC‐treated mice, with the cannabinoid antagonist, SR141716A increased the number and network correlation of active GC. These data provide physiological evidence of the involvement of cerebellar circuits in the adaptive changes occurring during chronic THC exposure and withdrawal.
Neuronal nitric oxide synthase expression in the mouse vomeronasal organ during prenatal development
Authors: Zancanaro Carlo , Merigo Flavia , Mucignat‐Caretta Carla , Cavaggioni Andrea 
Published: March 2003

AbstractThe presence and distribution of immunoreactivity for nitric oxide synthase type I and a panel of regulatory neuropeptides was investigated in the vomeronasal organ (VNO) of mouse embryos. Results show that nitric oxide synthase type I is first expressed in putative extrinsic nerve fibers reaching areas of vascular development at embryonic day 16 and in the vomeronasal nerve at embryonic day 15. Immunoreactivity for vasoactive intestinal peptide appears around developing vessels of the VNO during embryonic day 18. No immunoreactivity for atrial natriuretic peptide, substance P and calcitonin gene‐related peptide is present in the VNO. It is concluded that, in the mouse, nitric oxide synthesis is a precocious event in the development of peripheral and central neural vomeronasal structures, representing a very early step in the neurochemical maturation of the VNO.
Analysis of a slow desensitized state of recombinant adult‐type nicotinic acetylcholine receptor channels
Authors: Krampfl K. , Jahn K. , Cordes A.‐L. , Dengler R. , Bufler J. 
Published: March 2003

AbstractA characteristic feature of the kinetics of nicotinic acetylcholine receptor (nAChR) channels is fast and nearly complete desensitization with a time course between 10 and 100 ms and recovery from desensitization in the range of some hundred ms. In the present study we used a piezo‐driven system for ultra‐fast solution exchange, analysed the recovery from the fast desensitized state of mouse recombinant adult‐type nAChR channels and found no difference to that of embryonic‐type channels. By double pulse experiments with application of pulses with a saturating concentration of 1 mm acetylcholine (ACh) with increasing duration of the first pulse and a constant interval between pulses we detected a second slow desensitized state which was entered with a time constant of 2835 ms. Recovery from the slow desensitized state proceeded with a single exponential with a time constant of 16134 ms. The experimental data were interpreted by the addition of a transition from the desensitized state with two bound ACh molecules to a slow desensitized state to the well known circular kinetic scheme of activation and desensitization of nAChR channels. This slow desensitized state might play a role in muscle fatigue or in pathological states like myasthenic syndromes.
Comparative distribution of the mammalian mediator subunit thyroid hormone receptor‐associated protein (TRAP220) mRNA in developing and adult rodent brain
Authors: Galeeva Anastasia , Treuter Eckardt , Tuohimaa Pentti , Pelto‐Huikko Markku 
Published: March 2003

AbstractTRAP220 (thyroid hormone receptor‐associated protein) is a recently cloned nuclear receptor coactivator, which interacts with several nuclear receptors in a ligand‐dependent manner and stimulates transcription by recruiting the TRAP mediator complex to hormone responsive promoter regions. TRAP220 has been shown to interact with thyroid hormone receptors, vitamin D receptors, peroxisome proliferator‐activated receptors, retinoic acid receptors and oestrogen receptors. Thyroid hormone and retinoic acid play very important roles in brain development and they also influence adult brain. Using in situ hybridization we have examined expression of TRAP220 mRNA in the central nervous system during development and in adult rat and mouse brain. Expression of TRAP220 was seen already during early embryonic development in the epithelium of neural tube at E9 in mouse and at E12 in rat. At later stages of development the strongest signal was seen in different layers of cerebral neocortex, external germinal layer of cerebellum, differentiating fields of hippocampus and neuroepithelium, and a moderate signal was detected in basal ganglia, different areas of diencephalon and midbrain. In adult rat brain the signal was more restricted than during development. TRAP220 expression occurred mostly in the granular layer of cerebellar cortex, piriform cortex and hippocampal formation. The signal was found predominantly in neurons. Our work supports the assumption that TRAP220 plays an important role in growth and differentiation of central nervous system and may have a function in certain areas of adult brain.
Migration of LHRH neurons into the spinal cord: evidence for axon‐dependent migration from the transplanted chick olfactory placode
Authors: Murakami Shizuko , Arai Yasumasa 
Published: March 2003

AbstractIn the chick embryo, luteinizing hormone‐releasing hormone (LHRH) neurons originate in the olfactory placode and migrate along the olfactory nerve to the forebrain. In previous studies, we demonstrated that LHRH neurons followed the trigeminal nerve when the olfactory nerve was physically interrupted. To examine whether LHRH neurons posses the capacity to migrate along the different type of axons, the olfactory placode was transplanted into the base of the forelimb. Three to five days after the transplantation, LHRH neurons were detectable in the spinal nerve, the dorsal root ganglion, the sympathetic ganglion and the spinal cord. Double or triple labelling studies for LHRH, somatostatin and/or axonin‐1 showed that LHRH neurons entered the spinal nerve in contact with the olfactory axons, which are specifically immunoreactive to somatostatin. Migrating LHRH neurons continued to associate closely with the olfactory axons in the spinal nerve. However, some LHRH neurons often migrated along with the axonin‐1 positive spinal sensory axons, maintaining a distance from the olfactory axons. Furthermore, a few LHRH neurons were observed in the ventral root and the ventral funiculus independent of olfactory axons. As LHRH neurons were observed in the motor component of the spinal nerve, it is probable that LHRH neurons also invaded the spinal cord using the motor axons as a guiding substrate for their migration. These results suggest that the migration mode of LHRH neurons is axon dependent in the peripheral region, however, chemical identity with regard to axonal substrate choice for migration was not specified in the present study.
The effect of whole‐body tilt on sound lateralization
Authors: Lewald Jörg , Karnath Hans‐Otto 
Published: March 2003

AbstractThe effect of passive whole‐body tilt in the frontal plane on the lateralization of dichotic sound was investigated in human subjects. Pure‐tone pulses (1 kHz, 100 ms duration) with various interaural time differences were presented via headphones while the subject was in an upright position or tilted 45° or 90° to the left or right. Subjects made two‐alternative forced‐choice (left/right) judgements on the intracranial sound image. During body tilt, the auditory median plane of the head, computed from the resulting psychometric functions, was always shifted to the upward ear, indicating a shift of the auditory percept to the downward ear, that is, in the direction of gravitational linear acceleration. The mean maximum magnitude of the auditory shift obtained with 90° body tilt was 25 µs. On the one hand, these findings suggest a certain influence of the otolith information about body position relative to the direction of gravity on the representation of auditory space. However, in partial contradiction to previous work, which had assumed existence of a significant ‘audiogravic illusion’, the very slight magnitude of the present effect rather reflects the excellent stability in the neural processing of auditory spatial cues in humans. Thus, it might be misleading to use the term ‘illusion’ for this quite marginal effect.