bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mice deficient for the synaptic vesicle protein Rab3a show impaired spatial reversal learning and increased explorative activity but none of the behavioral changes shown by mice deficient for the Rab3a regulator Gdi1
Authors: D'Adamo Patrizia , Wolfer David P. , Kopp Caroline , Tobler Irene , Toniolo Daniela , Lipp Hans‐Peter 
Published: April 2004

AbstractRab proteins are small GTPases involved in intracellular trafficking. Among the 60 different Rab proteins described in mammals, Rab3a is the most abundant in brain, where it is involved in synaptic vesicle fusion and neurotransmitter release. Rab3a constitutive knockout mice (Rab3a−/−) are characterized by deficient short‐ and long‐term synaptic plasticity in the mossy fiber pathway and altered circadian motor activity, while no effects on spatial learning have been reported so far for these mice. The goals of this study were to analyse possible behavioral consequences of the lack of synaptic plasticity in the mossy fiber pathway using a broad battery of sensitive behavioral measures that has been used previously to analyse the behavior of Gdi1 mice lacking a protein thought to regulate Rab3a. Rab3a−/− mice showed normal acquisition but moderately impaired platform reversal learning in the water maze including reference memory and episodic‐like memory tasks. A mild deficit in spatial working memory was also observed when tested in the radial maze. Analysis of explorative behavior revealed increased locomotor activity and enhanced exploratory activity in open field, O‐maze, dark/light box and novel object tests. Spontaneous activity in normal home cage settings was unaffected but Rab3a−/− mice showed increased motor activity when the home cage was equipped with a wheel. No differences were found for delayed and trace fear conditioning or for conditioned taste aversion learning. Congruent with earlier data, these results suggest that Rab3a‐dependent synaptic plasticity might play a specific role in the reactivity to novel stimuli and behavioral stability rather than being involved in memory processing. On the other hand, the phenotypic changes in the Rab3a−/− mice bore no relation to the behavioral changes as observed in the Gdi1 mice. Such divergence in phenotypes implies that the putative synaptic interaction between Gdi1 and Rab3a should be reconsidered and re‐analysed.
Cocaine‐experienced rats exhibit learning deficits in a task sensitive to orbitofrontal cortex lesions
Authors: Schoenbaum Geoffrey , Saddoris Michael P. , Ramus Seth J. , Shaham Yavin , Setlow Barry 
Published: April 2004

AbstractAddictive drugs, such as cocaine, cause long‐lasting neural changes in prefrontal cortex. It has been hypothesized that these changes affect the behavioural control mediated by orbitofrontal cortex. To test this hypothesis, rats were given injections of cocaine (30 mg/kg/d, i.p.) or vehicle for 14 days and then trained after a 2‐week withdrawal period in an odor discrimination task sensitive to the effects of orbitofrontal cortex lesions. We found that cocaine‐treated rats, who demonstrated long‐lasting sensitization to the locomotor activating effects of cocaine, failed to show normal changes in response latency during discrimination learning and were also slower than controls to acquire serial reversals. These behavioural impairments are identical to the effects of orbitofrontal cortex lesions in this task and show that cocaine exposure in rats can cause long‐lasting effects on orbitofrontal‐dependent functions. Notably, these effects were not correlated with increases in locomotor activity linked to cocaine‐induced psychomotor sensitization observed before or after training, suggesting that the brain changes underlying the behavioural effects in the discrimination task are different from those mediating psychomotor sensitization.
The peptide sequence Arg‐Glu‐Arg, present in the amyloid precursor protein, protects against memory loss caused by Aβ and acts as a cognitive enhancer
Authors: Mileusnic R. , Lancashire C. L. , Rose S. P. R. 
Published: April 2004

AbstractAmino acid sequences containing the palindromic tripeptide RER, matching amino acids 328–330 of the amyloid precursor protein APP, when injected intracerebrally prior to or just after training, protect against memory loss induced by amyloid‐beta (Aβ) in a one‐trial passive avoidance task in the young chick. RER also acts as a cognitive enhancer, strengthening memory for a weak version of the task. N‐terminal acylation of RER protects it against rapid degradation, and AcRER is effective in restoring memory if administered peripherally. Biotinylated RER binds to chick neuronal perikarya in an APP‐displaceable manner via 66 and ≈ 110 kDa neuronal cell membrane proteins. We suggest that RER binding is likely to exert effects on memory retention via receptor‐mediated events that include activation of second messenger pathways. These findings suggest that RER and its derivatives may offer a novel approach to enhancing the neuroprotective effects of APP and alleviating the effects of memory loss in the early stages of Alzheimer's disease.
Functional MRI of the immediate impact of transcranial magnetic stimulation on cortical and subcortical motor circuits
Authors: Bestmann Sven , Baudewig Jürgen , Siebner Hartwig R. , Rothwell John C. , Frahm Jens 
Published: April 2004

AbstractRecent studies indicate that the cortical effects of transcranial magnetic stimulation (TMS) may not be localized to the site of stimulation, but spread to other distant areas. Using echo‐planar imaging with blood‐oxygenation‐level‐dependent (BOLD) contrast at 3 Tesla, we measured MRI signal changes in cortical and subcortical motor regions during high‐frequency (3.125 Hz) repetitive TMS (rTMS) of the left sensorimotor cortex (M1/S1) at intensities above and below the active motor threshold in healthy humans. The supra‐ and subthreshold nature of the TMS pulses was confirmed by simultaneous electromyographic monitoring of a hand muscle. Suprathreshold rTMS activated a network of primary and secondary cortical motor regions including M1/S1, supplementary motor area, dorsal premotor cortex, cingulate motor area, the putamen and thalamus. Subthreshold rTMS elicited no MRI‐detectable activity in the stimulated M1/S1, but otherwise led to a similar activation pattern as obtained for suprathreshold stimulation though at reduced intensity. In addition, we observed activations within the auditory system, including the transverse and superior temporal gyrus, inferior colliculus and medial geniculate nucleus. The present findings support the notion that re‐afferent feedback from evoked movements represents the dominant input to the motor system via M1 during suprathreshold stimulation. The BOLD MRI changes in motor areas distant from the site of subthreshold stimulation are likely to originate from altered synaptic transmissions due to induced excitability changes in M1/S1. They reflect the capability of rTMS to target both local and remote brain regions as tightly connected constituents of a cortical and subcortical network.
Addictive and non‐addictive drugs induce distinct and specific patterns of ERK activation in mouse brain
Authors: Valjent Emmanuel , Pagès Christiane , Hervé Denis , Girault Jean‐Antoine , Caboche Jocelyne 
Published: April 2004

AbstractA major goal of research on addiction is to identify the molecular mechanisms of long‐lasting behavioural alterations induced by drugs of abuse. Cocaine and delta‐9‐tetrahydrocannabinol (THC) activate extracellular signal‐regulated kinase (ERK) in the striatum and blockade of the ERK pathway prevents establishment of conditioned place preference to these drugs. However, it is not known whether activation of ERK in the striatum is specific for these two drugs and/or this brain region. We studied the appearance of phospho‐ERK immunoreactive neurons in CD−1 mouse brain following acute administration of drugs commonly abused by humans, cocaine, morphine, nicotine and THC, or of other psychoactive compounds including caffeine, scopolamine, antidepressants and antipsychotics. Each drug generated a distinct regional pattern of ERK activation. All drugs of abuse increased ERK phosphorylation in nucleus accumbens, lateral bed nucleus of the stria terminalis, central amygdala and deep layers of prefrontal cortex, through a dopamine D1 receptor‐dependent mechanism. Although some non‐addictive drugs moderately activated ERK in a few of these areas, they never induced this combined pattern of strong activation. Antidepressants and caffeine activated ERK in hippocampus and cerebral cortex. Typical antipsychotics mildly activated ERK in dorsal striatum and superficial prefrontal cortex, whereas clozapine had no effect in the striatum, but more widespread effects in cortex and amygdala. Our results outline a subset of structures in which ERK activation might specifically contribute to the long‐term effects of drugs of abuse, and suggest mapping ERK activation in brain as a way to identify potential sites of action of psychoactive drugs.
Corticotropin‐releasing factor and urocortin differentially modulate rat Purkinje cell dendritic outgrowth and differentiation in vitro
Authors: Swinny J. D. , Metzger F. , IJkema‐Paassen J. , Gounko N. V. , Gramsbergen A. , Van Der Want J. J. L. 
Published: April 2004

AbstractThe precise outgrowth and arborization of dendrites is crucial for their function as integrators of signals relayed from axons and, hence, the functioning of the brain. Proper dendritic differentiation is particularly resonant for Purkinje cells as the intrinsic activity of this cell‐type is governed by functionally distinct regions of its dendritic tree. Activity‐dependent mechanisms, driven by electrical signaling and trophic factors, account for the most active period of dendritogenesis. An as yet unexplored trophic modulator of Purkinje cell dendritic development is corticotropin‐releasing factor (CRF) and family member, urocortin, both of which are localized in climbing fibers. Here, we use rat organotypic cerebellar slice cultures to investigate the roles of CRF and urocortin on Purkinje cell dendritic development. Intermittent exposure (12 h per day for 10 days in vitro) of CRF and urocortin induced significantly more dendritic outgrowth (45% and 70%, respectively) and elongation (25% and 15%, respectively) compared with untreated cells. Conversely, constant exposure to CRF and urocortin significantly inhibited dendritic outgrowth. The trophic effects of CRF and urocortin are mediated by the protein kinase A and mitogen‐activating protein kinase pathways. The study shows unequivocally that CRF and urocortin are potent regulators of dendritic development. However, their stimulatory or inhibitory effects are dependent upon the degree of expression of these peptides. Furthermore, the effects of CRF and urocortin on neuronal differentiation and re‐modeling may provide a cellular basis for pathologies such as major depression, which show perturbations in the expression of these stress peptides.
Modulation of photic resetting in rats by lesions of projections to the suprachiasmatic nuclei expressing p75 neurotrophin receptor
Authors: Erhardt Christine , Galani Rodrigue , Jeltsch Hélène , Cassel Jean‐Christophe , Klosen Paul , Menet Jérôme S. , Pévet Paul , Challet Etienne 
Published: April 2004

AbstractThe suprachiasmatic nuclei of the hypothalamus (SCN) are the site of the master circadian clock in mammals. The SCN clock is mainly entrained by the light–dark cycle. Light information is conveyed from the retina to the SCN through direct, retinohypothalamic fibres. The SCN also receive other projections, like cholinergic fibres from basal forebrain. To test whether cholinergic afferents are involved in photic resetting, lesions of cholinergic projections were performed in rats with intracerebroventricular (i.c.v.) injections or intra‐SCN microinjections of 192 IgG‐saporin. When injected in the SCN, this immunotoxin destroys the cholinergic projections and retinohypothalamic afferents that express p75 low‐affinity nerve growth factor (p75NGF) receptors. The extent of lesions in the basal forebrain and SCN was assessed by acetylcholinesterase histochemistry, p75NGF receptor, choline acetyl‐transferase, calbindin‐D28K and VIP immunocytochemistry. The intra‐SCN treatment reduced light‐induced phase advances by 30%, and induced a complete loss of forebrain and retinal afferents expressing p75NGF receptors within the SCN and a decrease of forebrain cholinergic neurons, most likely those projecting to the SCN. The i.c.v. treatment reduced light‐induced phase advances by 40%, increased phase delays and led to extensive damage of forebrain p75NGF‐expressing neurons, while sparing half of the fibres expressing p75NGF receptors (retinal afferents?) in the SCN. Because the integrity of forebrain p75NGF‐expressing neurons appears to be critical in mediating the effects on light‐induced phase advances, we therefore suggest that anterior cholinergic projections expressing p75NGF receptors modulate the sensitivity of the SCN clock to the phase advancing effects of light.
Visual presentation of novel objects and new spatial arrangements of objects differentially activates the medial temporal lobe subareas in humans
Authors: Pihlajamäki Maija , Tanila Heikki , Könönen Mervi , Hänninen Tuomo , Hämäläinen Anne , Soininen Hilkka , Aronen Hannu J. 
Published: April 2004

AbstractA number of studies in rodents and monkeys report a distinction between the contributions of the hippocampus and perirhinal cortex to memory, such that the hippocampus is crucial for spatial memory whereas the perirhinal cortex has a pivotal role in perception and memory for visual objects. To determine if there is such a distinction in humans, we conducted a functional magnetic resonance imaging study to compare the medial temporal lobe responses to changes in object identity and spatial configurations of objects. We found evidence for the predicted distinction between hippocampal and perirhinal cortical activations, although part of the hippocampus was also activated by identification of novel objects. Additionally, an anterior‐posterior activation gradient emerged inside the hippocampus and parahippocampal cortex. The anterior hippocampus, perirhinal cortex and anterior parahippocampal cortex are involved in perception of contextually novel objects, whereas the posterior hippocampus and posterior parahippocampal cortex are involved in processing of novel arrangements of familiar objects. These results demonstrate that there is a functional dissociation between processing of novel object identities and new spatial locations of objects among the subregions of medial temporal lobe structures in humans also.
Influence of early postnatal rearing conditions on mesocorticolimbic dopamine and behavioural responses to psychostimulants and stressors in adult rats
Authors: Brake Wayne G. , Zhang Tie Yuan , Diorio Josie , Meaney Michael J. , Gratton Alain 
Published: April 2004

AbstractWhile many experiment with drugs, relatively few individuals develop a true addiction. We hypothesized that, in rats, such individual differences in the actions of addictive drugs might be determined by postnatal rearing conditions. To test this idea, we investigated whether stimulant‐ and stress‐induced activation of nucleus accumbens dopamine transmission and dopamine‐dependent behaviours might differ among adults rats that had been either repeatedly subjected to prolonged maternal separation or a brief handling procedure or left undisturbed (non‐handled) during the first 14 days of life. We found that, in comparison with their handled counterparts, maternally separated and non‐handled animals are hyperactive when placed in a novel setting, display a dose‐dependent higher sensitivity to cocaine‐induced locomotor activity and respond to a mild stressor (tail‐pinch) with significantly greater increases in nucleus accumbens dopamine levels. In addition, maternally separated animals were found to sensitize to the locomotor stimulant action of amphetamine when repeatedly stressed under conditions that failed to sensitize handled and non‐handled animals. Finally, quantitative receptor autoradiography revealed a lower density of nucleus accumbens‐core and striatal dopamine transporter sites in maternally separated animals. Interestingly, we also found greatly reduced D3 dopamine receptor binding and mRNA levels in the nucleus accumbens‐shell of handled animals. Together, these findings provide compelling evidence that disruptions in early postnatal rearing conditions can lead to profound and lasting changes in the responsiveness of mesocorticolimbic dopamine neurons to stress and psychostimulants, and suggest a neurobiological basis for individual differences in vulnerability to compulsive drug taking.
Increased expression of TRPV1 receptor in dorsal root ganglia by acid insult of the rat gastric mucosa
Authors: Schicho Rudolf , Florian Waltraud , Liebmann Ingrid , Holzer Peter , Lippe Irmgard Th. 
Published: April 2004

AbstractIt is still unknown which receptors of peripheral sensory pathways encode and integrate an acid‐induced nociceptive event in the gastric mucosa. The transient receptor potential vanilloid receptor 1 (TRPV1) and the acid‐sensing ion channel 3 (ASIC3) are two nociception‐related receptors. Here we investigated (i) to what extent these receptors are distributed in stomach‐innervating neurons of dorsal root and nodose ganglia, using immunohistochemistry and retrograde tracing, and (ii) whether their expression is altered in response to a noxious acid challenge of the stomach. We also explored the presence of TRPV1 in the gastric enteric nervous system because of its possible expression by intrinsic sensory neurons. Most stomach‐innervating neurons in nodose ganglia were immunoreactive for TRPV1 (80%) and ASIC3 (75%), these results being similar in the dorsal root ganglia (71 and 82%). RT‐PCR and Western blotting were performed up to 6 h after oral application of 0.5 m HCl to conscious rats. TRPV1 protein was increased in dorsal root but not in nodose ganglia whereas TRPV1 and ASIC3 mRNAs remained unchanged. TRPV1 mRNA was detected in longitudinal muscle–myenteric plexus preparations of control stomachs and was not altered by the acid challenge. Combined vagotomy and ganglionectomy abolished expression of TRPV1, indicating that it may derive from an extrinsic source. In summary, noxious acid challenge of the stomach increased TRPV1 protein in spinal but not vagal or intrinsic sensory afferents. The TRPV1 receptor may be a key molecule in the transduction of acid‐induced nociception of the gastric mucosa and a mediator of visceral hypersensitivity.
Distinct mechanisms of bidirectional activity‐dependent synaptic plasticity in superficial and deep layers of rat entorhinal cortex
Authors: Solger Jörg , Wozny Christian , Manahan‐Vaughan Denise , Behr Joachim 
Published: April 2004

AbstractThe entorhinal cortex plays a key role in processing memory information in the brain; superficial layers relay information to, and deep layers receive information from, the hippocampus. The cellular mechanisms of memory are thought to include a number that produce long‐term potentiation (LTP) and depression (LTD) of synaptic strength. Our work presents evidence that LTP and LTD occur simultaneously at memory‐relevant synapses. We report here that low frequency stimulation generates NMDA receptor‐dependent LTD in Wistar rat superficial (layers II and III), and LTP in the deep entorhinal cortex layers (layers V and VI). LTP in deep layers is masked by simultaneously occurring voltage‐gated calcium channel‐dependent LTD. Our data support a novel mechanism for the sliding‐threshold (BCM) model of synaptic plasticity: The sliding thresholds for induction of LTP and LTD in entorhinal cortex deep layers will be driven by the relative activation state of NMDA receptors and voltage‐gated calcium channels. The co‐expression of LTD and LTP at presynaptic sites in the entorhinal cortex deep layers reveals an intriguing mechanism for differential processing of synaptic information, which may underlie the vast dynamic capacity for information storage by this cortical structure.
Effects of inescapable stress on LTP in the amygdala versus the dentate gyrus of freely behaving rats
Authors: Vouimba Rose‐Marie , Yaniv Dan , Diamond David , Richter‐Levin Gal 
Published: April 2004

AbstractStress impairs hippocampal long‐term potentiation (LTP), a model of synaptic plasticity that is assumed to underlie memory formation. In the amygdala, little is known about the effects of stress on LTP, or about its longevity. Here we assessed the ability of entorhinal cortex (EC) stimulation to induce LTP simultaneously in the basal amygdaloid nucleus (B) and in the dentate gyrus (DG) of freely behaving Wistar rats. We also tested whether LTP persists over days. Once established, we investigated the effects of acute vs. repeated inescapable stressful experiences on LTP in both structures. Results show that B, like DG, sustained LTP for 7 days. Furthermore, a single exposure to moderate stress facilitated LTP in B but did not affect DG LTP. Stress re‐exposure inhibited LTP in DG but only long‐lasting LTP (>3 days) in B. Behaviourally, animals exhibited a higher immobility when re‐exposed to the stressor than with a single/first exposure. These data support a role for B in memory storage. Furthermore, they support a differential involvement of the amygdala and hippocampus in memory formation and storage depending on the emotional characteristics of the experience.
How do target predictability and precueing affect the production of express saccades in monkeys?
Authors: Schiller Peter H. , Haushofer Johannes , Kendall Geoffery 
Published: April 2004

AbstractThe extent to which target predictability and precueing affect express saccade generation was determined in Rhesus monkeys. Target predictability, as manipulated by the probability with which targets appeared at various locations, had a strong influence on express saccade generation. Pre‐cueing the location of the appearance of an impending single target with an identical stimulus was effective in increasing express saccade generation when there was a gap of 50–150 ms between fixation spot termination and target onset. However, precueing was not effective when the gap time was set to 0 ms in the single target task, when several simultaneous targets appeared requiring a visual discrimination to be made using an oddity task, or when the precue was not identical to the target. These findings indicate that express saccades are facilitated by a restricted set of conditions that increase the predictability of target location and identity.