bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dysfunctional regulation of αCaMKII and syntaxin 1B transcription after induction of LTP in the aged rat
Authors: Davis S. , Salin H. , Helme‐Guizon A. , Dumas S. , Stéphan A. , Corbex M. , Mallet J. , Laroche S. 
Published: March 2003

AbstractSyntaxin 1B and αCaMKII are two genes that are upregulated after the induction of LTP and appear to underlie different mechanisms of synaptic plasticity. αCaMKII is directly implicated in strengthening the synapses that have been modified, whereas syntaxin 1B has been implicated in a mechanism for the propagation of synaptic plasticity within neural circuits. In these experiments we have investigated whether the regulation of these genes is altered after the induction of LTP in aged rats. We found, three hours after the induction of LTP in the dentate gyrus, that aged rats could be subgrouped into those in which LTP was maintained and those in which LTP had decayed back to basal levels. Both genes were upregulated in young adult rats, whereas there was a differential pattern of LTP‐induced expression in the aged rats. Dendritic αCaMKII was upregulated in aged rats only when LTP was maintained. In contrast, regulation of syntaxin 1B and αCaMKII was absent in the granule cell bodies of the aged rats regardless of whether LTP was maintained or not. These results suggest that molecular mechanisms implicated in two aspects of hippocampal synaptic plasticity malfunction during normal ageing and therefore may have some contributory role in the decline in memory function routinely observed in ageing.
Can a motion‐blind patient reach for moving objects?
Authors: Schenk Thomas , Mai Norbert , Ditterich Jochen , Zihl Josef 
Published: March 2003

AbstractIt has been claimed that the visual brain is organized in two separate processing streams for spatial vision: one for perception and one for action. To determine whether motion vision is also divided into vision for action and for perception we examined the interceptive behaviour of the motion‐blind patient LM. The task for LM and three age‐matched control subjects was to reach‐and‐grasp for an object that moved away. Three experiments were conducted to examine the effects on perfomance of target speed (Expt 1), observation time (Expt 2) and visual feedback (Expt 3). As LM is only able to reach for objects which move at 0.5 m/s or less, her performance is inferior to that of controls who can reach for objects moving at 1.0 m/s, but it is better than would be expected from her performance in psychophysical experiments on her motion vision. Kinematic analysis of LM's reaching movements showed that she adapted the speed of her moving hand to the speed of the target but only when full vision was available. In contrast to normal subjects, LM required long observation times and vision of her moving hand to produce successful reaching responses. Thus, the impairment of both perception and action in LM suggests that the motion area MT/V5 is located at an early stage of the extrastriate hierarchy and provides input to both the perception and the action processing streams.
Different functions of fetal and adult AChR subtypes for the formation and maintenance of neuromuscular synapses revealed in ε‐subunit‐deficient mice
Authors: Schwarz Holger , Giese Günter , Müller Holger , Koenen Michael , Witzemann Veit 
Published: March 2003

AbstractMice deficient in ε‐subunits of the acetylcholine receptor (AChR) channel die prematurely due to severe AChR deficiency that leads to the progressive reduction in AChR density at the neuromuscular endplate [Witzemann, V., Schwarz, H., Koenen, M., Berberich, C., Villarroel, A., Wernig, A., Brenner, H.R. & Sakmann, B. (1996) Proc. Natl Acad. Sci. USA, 93, 13286–13291]. The mice may serve as a model for studying AChR‐related myasthenic diseases. The postnatal development of the subsynaptic apparatus takes place in the absence of the adult type, ε‐subunit‐containing receptors which normally replace the fetal γ‐subunit‐containing receptors. During later development the secondary folds of the postsynaptic membrane disappear concomitant with the decrease in AChR density, so that the flattened‐out membrane with its remaining nicotinic receptors is in close proximity to the subsynaptic cytoplasmatic compartment and the subsynaptic myonuclei. The decrease in AChR concentration is correlated with a decrease of postsynaptic rapsyn, but has less effect on agrin, a neuronally released aggregating factor for AChRs. Thus, despite the presence of agrin at the synapse, AChR expression is not maintained at the level required to stabilize normal synaptic structure comprising secondary postsynaptic membrane folds. Collectively the results suggest that the postnatal switch from the global, activity‐sensitive γ‐subunit gene transcription to the synapse‐specific, activity‐independent ε‐subunit gene transcription is not required for the formation and differentiation of synapses but is essential for the maintenance of the highly organized structure of the neuromuscular endplate.
Transcriptional and post‐transcriptional regulation of a brain growth protein: regional differentiation and regeneration induction of GAP‐43
Authors: Namgung Uk , Routtenberg Aryeh 
Published: March 2003

AbstractDuring axonal regeneration synthesis of different growth‐associated proteins is increased. As yet there is no clear picture of the specific contribution made by the transcriptional and post‐transcriptional machinery that provides the gene products necessary for process outgrowth. Here we focus our study on the transcriptional processes in neurons by using intron‐directed in situ hybridization to the primary transcript of a brain growth protein GAP‐43. In most brain regions, levels of primary transcript expression of GAP‐43 were highly correlated with levels of its mRNA. However, there were notable dissociations: in hippocampal granule cells, high levels of primary transcript were evident yet no GAP‐43 mRNA was detected. In locus coeruleus the reverse was true; there were high levels of GAP‐43 mRNA but no detectable primary transcript. A primary transcript antitermination mechanism is proposed to explain the first dissociation, and a post‐transcriptional mRNA stabilization mechanism to explain the second. Transcriptional activation during nerve regeneration was monitored by assessing primary transcript induction of GAP‐43 in mouse facial motor neurons. This induction, as well as its mRNA, was restricted to the side of the facial nerve crush. Increases were first observed at 24 h with a rapid increase in both measures up to 3 days. To our knowledge, this is the first in vivo evidence demonstrating transcriptional activation of a brain growth protein in regenerating neurons. The present study points to the GAP‐43 transcriptional mechanism as a key determinant of GAP‐43 synthesis. Along with the recruitment of post‐transcriptional mechanisms, such synthesis occurs in response to both intrinsic developmental programs and extrinsic environmental signals.
Recovery of emotional behaviour in neural cell adhesion molecule (NCAM) null mutant mice through transgenic expression of NCAM180
Authors: Stork O. , Welzl H. , Wolfer D. , Schuster T. , Mantei N. , Stork S. , Hoyer D. , Lipp H. ‐P. , Obata K. , Schachner M. 
Published: March 2003

AbstractIn the present study we further investigate functions of the neural cell adhesion molecule (NCAM) in the mature central nervous system and its implications for animal behaviour. To this end we generated transgenic mice expressing the major NCAM isoform with the largest cytoplasmic domain, NCAM180, under control of a promoter for the small form neurofilament gene. Transgenic mice were also bred with mice deficient in endogenous NCAM (Ncam–/– mice) so that effects of NCAM180 could be analysed in the presence and absence of endogenous NCAM. While overexpression of transgenic NCAM180 was without apparent behavioural or morphological effect, its expression in Ncam–/– mice counteracted NCAM ablation‐induced aggressive, anxiety‐like and antidepressant‐like behaviour. It furthermore prevented a hypersensitivity of Ncam–/– mice to the anxiolytic serotonin1A (5‐HT1A) receptor agonist buspirone. Such recovery of emotional behaviour and behavioural 5‐HT1A response occurred in spite of misdevelopment of the olfactory bulb and hippocampus that is characteristic of Ncam–/– mice, and without an apparent change in the expression of 5‐HT1A binding sites in the brain. Hippocampus‐ and amygdala‐dependent learning, though disturbed in Ncam–/– mice, remained unaffected by the transgenic NCAM180. We suggest an involvement of NCAM180‐mediated cell recognition processes in the serotonergic modulation of emotional behaviour in adult mice.
Evidence for coassembly of mutant GABACρ1 with GABAAγ2S, glycine α1 and glycine α2 receptor subunits in vitro
Authors: Pan Zhuo‐Hua , Zhang Dongxian , Zhang Xishan , Lipton Stuart A. 
Published: March 2003

AbstractFunctional coassembly of γ‐aminobutyric acid (GABA)Cρ1 subunits with GABAA (α1, β2, and γ2S) or glycine (α1, α2, and β) subunits was examined using two‐electrode voltage‐clamp recordings in the Xenopus laevis oocyte expression system. To facilitate this study, we took advantage of the unique gating and pharmacological properties of two mutant ρ1 subunits, ρ1(T314A) and ρ1(T314A/L317A). When the ρ1(T314A) subunit was coexpressed with GABA γ2S, glycine α1 or glycine α2 subunits, GABA response properties were different from those of homomeric ρ1(T314A) receptors. Additionally, the sensitivity of heteromeric ρ1(T314A) and γ2S receptors to picrotoxinin (PTX) blockade of GABA‐evoked responses was altered compared to that of homomeric ρ1(T314A) receptors. Changes in GABA response properties and picrotoxinin sensitivity were also observed when ρ1(T314A) subunits were coexpressed with wild‐type ρ1 subunits. When ρ1(T314A/L317A) subunits were coexpressed with GABA γ2S, glycine α1 or glycine α2 subunits, suppression by GABA of spontaneously active current was reduced compared to that of homomeric ρ1(T314A/L317A) receptors. Recovery of the spontaneous current from inhibition by GABA for GABA ρ1(T314A/L317A)/γ2S heteromeric receptors displayed an additional component. Coinjection of wild‐type ρ1 with γ2S cRNAs at a ratio of 1 : 1 resulted in a > 10‐fold reduction in GABA‐evoked current. Furthermore, coexpression of wild‐type ρ1 and γ2S subunits was found to shift the GABA dose–response curve. Our results provide functional evidence that the GABACρ1 subunit can coassemble with the GABAAγ2S subunit, and, at least in its mutated form, ρ1 can also form heteromeric receptors with glycine α1 or α2 subunits in vitro.
Unrelated course of subthalamic nucleus and globus pallidus neuronal activities across vigilance states in the rat
Authors: Urbain Nadia , Gervasoni Damien , Soulière Fabienne , Lobo Letícia , Rentéro Nicolas , Windels François , Astier Bernadette , Savasta Marc , Fort Patrice , Renaud Bernard , Luppi Pierre‐Hervé , Chouvet Guy 
Published: March 2003

AbstractThe pallido‐subthalamic pathway powerfully controls the output of the basal ganglia circuitry and has been implicated in movement disorders observed in Parkinson's disease (PD). To investigate the normal functioning of this pathway across the sleep–wake cycle, single‐unit activities of subthalamic nucleus (STN) and globus pallidus (GP) neurons were examined, together with cortical electroencephalogram and nuchal muscular activity, in non‐anaesthetized head‐restrained rats. STN neurons shifted from a random discharge in wakefulness (W) to a bursting pattern in slow wave sleep (SWS), without any change in their mean firing rate. This burst discharge occurred in the 1–2 Hz range, but was not correlated with cortical slow wave activity. In contrast, GP neurons, with a mean firing rate higher in W than in SWS, exhibited a relatively regular discharge whatever the state of vigilance. During paradoxical sleep, both STN and GP neurons increased markedly their mean firing rate relative to W and SWS. Our results are not in agreement with the classical ‘direct/indirect’ model of the basal ganglia organization, as an inverse relationship between STN and GP activities is not observed under normal physiological conditions. Actually, because the STN discharge pattern appears dependent on coincident cortical activity, this nucleus can hardly be viewed as a relay along the indirect pathway, but might rather be considered as an input stage conveying corticothalamic information to the basal ganglia.
Ultrastructural localization of mint1 at synapses in mouse hippocampus
Authors: Okamoto Masaya , Matsuyama Tomohiro , Sugita Minoru 
Published: March 2003

AbstractMint1 and mint2 were isolated in the course of seeking the protein ligands to munc18–1, a neuronal protein essential for synaptic vesicle exocytosis. The mint family of proteins has been highly conserved in the course of evolution, being retained from C. elegans to mammals. Several lines of biochemical and genetic evidence have suggested that mint1 and LIN‐10, its homologue in C. elegans, function at synapses in the brain. Because the precise subcellular location of mint1 is incompletely known, we used immunostaining to examine the distribution of mint1 in the mouse brain including ultrastructural localization in synapses. Strong, finely punctate mint1 immunolabeling was detected throughout the brain, including cerebral cortex, striatum, hippocampus, thalamus, basal ganglia and cerebellum. At the most synapses in the molecular layer, mint1 was particularly abundant at the active zone and to a lesser extent in association with synaptic vesicles in the presynaptic terminals. In contrast, a very few synapses showed mint1 immunoreactivity in the postsynaptic density and there was no synapse double‐positive in presynaptic and postsynaptic terminals. Mint1 distribution within presynaptic terminals overlapped that of munc18–1. These localization results are consistent with previously demonstrated biochemical interactions and strongly support functions of mint1 in synaptic vesicle exocytosis and synaptic organization in the central nervous system.
Volume‐regulated anion channels do not contribute extracellular adenosine during the hypoxic depression of excitatory synaptic transmission in area CA1 of rat hippocampus
Authors: Pearson Tim , Frenguelli Bruno G. 
Published: March 2003

AbstractWe investigated whether volume‐regulated anion channels (VRACs) contributed to the accumulation of extracellular adenosine during hypoxia in area CA1. The rapid hypoxic depression of the fEPSP was greatly attenuated by the selective adenosine A1 receptor antagonist DPCPX (50 nm), but not affected by the VRAC blockers tamoxifen (10–30 μm) or DNDS (1 mm). Our data argue against the efflux of adenosine per se or its precursor ATP through VRACs as making a significant contribution to extracellular adenosine during the early stages of hypoxia.
Melatonin sees the light: blocking GABA‐ergic transmission in the paraventricular nucleus induces daytime secretion of melatonin
Authors: Kalsbeek Andries , Garidou Marie‐Laure , Palm Inge F. , Van Der Vliet Jan , Simonneaux Valérie , Pévet Paul , Buijs Ruud M. 
Published: March 2003

AbstractDespite a pronounced inhibitory effect of light on pineal melatonin synthesis, usually the daily melatonin rhythm is not a passive response to the surrounding world. In mammals, and almost every other vertebrate species studied so far, the melatonin rhythm is coupled to an endogenous pacemaker, i.e. a circadian clock. In mammals the principal circadian pacemaker is located in the suprachiasmatic nuclei (SCN), a bilateral cluster of neurons in the anterior hypothalamus. In the present paper we show in the rat that bilateral abolition of γ‐aminobutyric acid (GABA), but not vasopressin, neurotransmission in an SCN target area, i.e. the paraventricular nucleus of the hypothalamus, during (subjective) daytime results in increased pineal melatonin levels. The fact that complete removal of the SCN results in a pronounced increase of daytime pineal mRNA levels for arylalkylamine N‐acetyltransferase (AA‐NAT), i.e. the rate‐limiting enzyme of melatonin synthesis, further substantiates the existence of a major inhibitory SCN output controlling the circadian melatonin rhythm.
Close linkage between calcium/calmodulin kinase II α/β and NMDA‐2A receptors in the lateral amygdala and significance for retrieval of auditory fear conditioning
Authors: Moriya Takahiro , Kouzu Yasuko , Shibata Shigenobu , Kadotani Hiroshi , Fukunaga Kohji , Miyamoto Eishichi , Yoshioka Tohru 
Published: March 2003

AbstractThe general mechanism underlying memory and learning is an area under intense investigation and debate, yet this mechanism still remains elusive. Auditory fear conditioning (when a tone is paired with a foot shock) is a simple associative form of learning for which many mechanistic details are known. Lesions of the lateral/basolateral nuclei of the amygdala result in the selective impairment of fear conditioning, indicating that this is a key region for this type of learning. Fear conditioning induces a lasting synaptic potentiation in the lateral nuclei of the amygdala. In addition, recent results from several laboratories suggest that N‐methyl‐ d‐aspartate (NMDA) receptor activation in the amygdala is required for the acquisition and expression of cue‐conditioned fear responses using several kinds of antagonists. Little is known, however, about the signal transduction pathway and molecular substrate underlying fear conditioning. Here we use NMDA receptor‐deficient mice to demonstrate that calmodulin‐dependent kinase II, CaMKIIβ, and CaMKIIα activation involves the NR2A subunit in the lateral/basolateral amygdala during memory retrieval following auditory fear conditioning. These results suggest that auditory fear conditioning involves a close linkage between NMDA2A receptors and the CaMKII cascade.
Age‐ and species‐dependent maturation of synaptic transmission in the superficial superior colliculus
Authors: White Anne‐Marie , Platt Bettina 
Published: March 2003

AbstractBoth neonatal maturity and postnatal maturation are known to be species dependent. For instance, guinea pigs are born with their eyes open, while eye opening takes place 2 weeks after birth in rats. Moreover, several abnormalities have been observed in albino compared to pigmented species. The pigment melanin is proposed to play a protective role and its absence is thought to contribute to neuronal deficits. In the present study, we aimed to investigate functional differences in synaptic transmission in the visual, superficial layers of the superior colliculus (SC) of albino and pigmented rats and pigmented guinea pigs, at eye opening and 1 month after birth. This was achieved by analysing evoked field excitatory postsynaptic potentials (fEPSPs) in vitro, and by investigating the ability of these responses to express γ‐aminobutyric acid (GABA)‐induced long‐term potentiation (LTPG), an enduring increase in synaptic efficacy resulting from bath application of GABA.Guinea pigs did not show any obvious differences with respect to overall fEPSP characteristics and synaptic plasticity at both ages studied, indicating that maturation must have occurred prenatally. Rats, however, underwent synaptic maturation and refinement to produce stronger fEPSPs and a more robust level of synaptic plasticity 1 month after birth compared to the conditions at eye opening. The state of pigmentation was found to have a crucial influence, with albino rats showing less enhancement of the strength of synaptic transmission in the SC.It can therefore be concluded that profound developmental differences in pre‐ and postnatal maturation of the superficial SC exist between guinea pigs and rats, and that the state of pigmentation is a crucial factor in this process.
Assessment of behavioural recovery following spinal cord injury in rats
Authors: Muir Gillian D. , Webb Aubrey A. 
Published: March 2003

AbstractBehavioural recovery is one of the primary goals of therapeutic intervention in animal models of disease. It is necessary, therefore, to have the means with which to quantify pertinent behavioural changes in experimental animals. Nevertheless, the number and diversity of behavioural measures which have been used to assess recovery after experimental interventions often makes it difficult to compare results between studies. The present review attempts to integrate and categorize the wide variety of behavioural assessments used to measure recovery in spinal‐injured rats. These categories include endpoint measures, kinematic measures, kinetic measurements, and electrophysiological measurements. Within this categorization, we discuss the advantages and disadvantages of each type of measurement. Finally, we make some recommendations regarding the principles for a comprehensive behavioural analysis after experimental spinal cord injury in rats.
Long‐term spatial memory in rats with hippocampal lesions
Authors: Ramos Juan M. J. 
Published: March 2003

AbstractIn animal models of human amnesia, using lesion methods, it has been difficult to establish the role played by the hippocampus in the formation of long‐term spatial knowledge. For example, lesions sustained after acquisition have generally produced a flat retrograde amnesia for spatial information. These results have not made it possible to dissociate the participation of the hippocampus in retrieval/performance processes from its participation in consolidation/retention. The present study was designed to investigate if electrolytic hippocampal lesions made before training lead to a deficit in the long‐term retention of spatial knowledge when the rats show equal performance levels during the acquisition. Results show that lesioned rats learn a place response just as well as the control rats when, during the training, an intramaze cue orients the animal in its navigation towards the goal arm. One day after reaching criterion, lesioned and control rats remember the task perfectly during a transfer test in which the intramaze signal used previously is not present. However, 24 days later, the hippocampal animals manifest a profound deficit in the retention of the spatial information. When the spatial task learned during the acquisition phase requires only the use of a guidance strategy, control and lesioned animals show the same level of performance during the training phase and the same degree of retention during the retraining phase 24 days after criterion. Taken together, these results suggest that the hippocampus plays a crucial role in long‐term retention of allocentric spatial information.